View source for Biology:HLA DR3-DQ2

{{Infobox multi-gene haplotype
 | haplotype = HLA DR3-DQ2
 | image = HLA-mini.png
 | image_source = HLA region on chromosome 6
 | chromosome = 6 
 | location = 6p21.3
 | variable = 
 | alias = HLA DRB1*0301:DQA1*0501:DQB1*0201
 | othertype = Serotype
 | loci1name = [[Biology:HLA-DR|HLA-DR]]
 | loci1rows = 3
 | gene1name = HLA-DRA
 | gene1var = <span class=plainlinks>[http://www.ebi.ac.uk/cgi-bin/imgt/hla/get_allele.cgi?DRA*0102 *0101]</span>
 | type1var = 
 | loci2name = [[Biology:HLA-DR|HLA-DR]]
 | loci2rows = 
 | gene2name = HLA-DRB1
 | type2var = [[Biology:HLA-DR3|DR3]]
 | loci3name = 
 | loci3rows = 
 | gene3name = [[Biology:HLA-DRB3|HLA-DRB3]]
 | type3var = [[Biology:HLA-DR52|DR52]]
 | loci4name = [[Biology:HLA-DQ|HLA-DQ]]
 | loci4rows = 2
 | gene4name = HLA-DQA1
 | type4var = 
 | loci5name = 
 | loci5rows = 
 | gene5name = HLA-DQB1
 | type5var = [[Biology:HLA-DQ2|DQ2]]
 | popMax = Sardinia
 | freqMax = 22%
 | length = 300
 | haplotype1 = [[Biology:HLA-DQ2#DQ2.5|DQ2.5]]
 | disease1 = [[Medicine:Coeliac disease|Coeliac disease]]
 | haplotype2 = DR3-DQ2
 | disease2 = Juvenile diabetes
 | haplotype3 = DR3-DQ2
 | disease3 = [[Medicine:Sarcoidosis|Sarcoidosis]]
 | NumLoci = 5
 }}

'''HLA DR3-DQ2''' is double [[Biology:Serotype|serotype]] that specifically recognizes cells from individuals who carry a multigene [[Biology:Human leukocyte antigen|HLA]] [[Biology:HLA-DR|DR]], [[Biology:HLA-DQ|DQ]] haplotype.
Certain HLA DR and DQ genes have known involvement
in autoimmune diseases. [[Biology:HLA-DR3|DR3]]-[[Biology:HLA-DQ2|DQ2]], a multigene 
haplotype, stands out in prominence because it is a factor in several prominent diseases, namely [[Medicine:Coeliac disease|coeliac disease]] and juvenile diabetes.  In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes [[Biology:HLA-DQ2#DQ2.5|DQ2.5]]cis isoform of [[Biology:HLA-DQ|HLA-DQ]], this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

The frequency of both diseases changes with respect to both the environment (diet) and the frequency of the DR3-DQ2. With coeliac disease risk is increased with the consumption of ''[[Biology:Triticeae|Triticeae]]'' glutens, and this also increases risk in juvenile diabetes whereas other cereals also appear to play a role. More importantly the risk of disease is greatest in homozygotes and linear increases in haplotype resulting in several fold increases of disease risk. This increased risk is most prominent in a rare cancer, enteropathy associated T-cell [[Medicine:Lymphoma|lymphoma]]. HLA-DR3-DQ2 is found in [[Biology:HLA A1-B8-DR3-DQ2|HLA A1-B8-DR3-DQ2]]  haplotype in  Northern Europeans (including the British Ilse, Ireland, Iceland).

==Genetic Linkage==
'''HLA DR3-DQ2'''  is the serotypic representation of a HLA-DRB1:DQA1:DQB1
cis-chromosomal haplotype on human [[Biology:Chromosome 6|6p]]21.3 in a region known as the [[Biology:Human leukocyte antigen|HLA]] complex. The DR3-DQ2 haplotype is notable because of the very strong linkage between genes that extends into the [[Biology:HLA-A|HLA-A]], -[[Biology:HLA-B|B]] and -[[Biology:HLA-C|C]] regions of the HLA gene complex in northern and northwestern Europe. The linked haplotype is [[Biology:HLA A1-B8-DR3-DQ2|HLA A1-B8-DR3-DQ2]] (AH8.1 in the most recent literature)

Because of its strong linkage disequilibrium, each of the genes in the haplotype are markers for probable presence of adjacent genes. However serotyping does not recognize genes, but clusters of gene products. For example, DQ2 recognizes both DQB1*0201, DQB1*0202, DQB1*0203. DQB1*0202 is not genetically linked to DQA1*0501 and its cis-haplotype isoform infrequently mediates coeliac disease or type 1 diabetes. For serotypic identification of the DQ2.5cis isoform requires the DR3 (or [[Biology:HLA-DR17|HLA-DR17]] or [[Biology:HLA-DR18|HLA-DR18]]) and DQ2 serotypes.

An example of phenotypes that can mediate CD and T1D, the DR3-DQ2/X serotypes and the DR5-DQ7/DR7-DQ2 serotypes can mediate celiac disease with equal efficiency but the DR5-DQ7/DR7-DQ2 cannot mediate T1D as successfully as DR4-DQ8 or DR3-DQ2 (X is not DR3-DQ2 or DR7-DQ2).

==Distribution==
'''HLA DR3-DQ2''' is not spread evenly among humans. It has a substantially higher frequency in the western world, except indigenous Native American (see tables). It is virtually absent in some Asian populations. It current world distribution suggest that it spread from Africa with a wave that spread late in human evolution which reached central Asia more recently, a possibility is that it spread with agrarian cultures that migrated from Africa. [Note some population test DR3 or DQA1:DQB1, the DR3-DQ2 serotype is generally synonymous in frequency with DQ2.5]

===Frequencies in Africa===
{| border="0" cellspacing="0" cellpadding="1" align="left" style="text-align:center; margin-right: 1em;  border:1px #bbbbff solid; background:#f8f8ff; "
|+ Table 2.1.1 DR3 and DQ2.5 levels in Africans (given as frequency in %)
|- style = "background:#eeeeff" 
! style="color:#eeeeff" | h !! align="left" width="100"|Reference  
! style="font-size:90%" width="40" |DRB1 
! style="font-size:90%" width="40"|DQA1 
! style="font-size:90%" width="40"|DQB1 
! style="font-size:90%" |Haplo.
! width="60" style="font-size:80%"|Estimated
|- style = "background:#eeeeff" 
! style="color:#eeeeff" | h !! align="left"| Population  !!  0301 !! 0501  !! 0201 !! style="font-size:90%" |DR3-DQ2 !!  DQ2.5
|-
|align="right" style="background:#f4f4ff" | <ref name = "Morocco_SoussII">{{cite journal |vauthors=Izaabel H, Garchon H, Caillat-Zucman S, Beaurain G, Akhayat O, Bach J, Sanchez-Mazas A | title = HLA class II DNA polymorphism in a Moroccan population from the Souss, Agadir area. | journal = Tissue Antigens | volume = 51 | issue = 1 | pages = 106–10 | year = 1998 | pmid = 9459511 | doi = 10.1111/j.1399-0039.1998.tb02954.x| url = https://archive-ouverte.unige.ch/unige:17063 }}</ref>
| align="left" style="background:#f4f4ff"  | Suoss (Morocco)
| 17.3 || 28.6* ||  37.8* || 17.3 
! style="background:#fafaff" | 17.3
|-
|align="right" style="background:#f4f4ff" | <ref name = "NMoroccoBerberI">{{cite journal |vauthors=Piancatelli D, Canossi A, Aureli A, Oumhani K, Del Beato T, Di Rocco M, Liberatore G, Tessitore A, Witter K, El Aouad R, Adorno D | title = Human leukocyte antigen-A, -B, and -Cw polymorphism in a Berber population from North Morocco using sequence-based typing. | journal = Tissue Antigens | volume = 63 | issue = 2 | pages = 158–72 | year = 2004 | pmid = 14705987 | doi = 10.1111/j.1399-0039.2004.00161.x}}</ref>
|align="left" style="background:#f4f4ff;" | Berbers
| 14.8 || 27.3* || 29.7*  ||  14.3
! style="background:#fafaff" | 14.3
|-
|align="right" style="background:#f4f4ff" | <ref name = "TunisI&II">{{cite journal |vauthors=Hajjej A, Kâabi H, Sellami M, Dridi A, Jeridi A, El borgi W, Cherif G, Elgaâïed A, Almawi W, Boukef K, Hmida S | title = The contribution of HLA class I and II alleles and haplotypes to the investigation of the evolutionary history of Tunisians. | journal = Tissue Antigens | volume = 68 | issue = 2 | pages = 153–62 | year = 2006 | pmid = 16866885 | doi = 10.1111/j.1399-0039.2006.00622.x}}</ref>
|align="left" style="background:#f4f4ff;" |  Tunis (Tunisia)
| 15.1     ||       || 15.9   ||  
! style="background:#fafaff" | 14.1
|-
|align="right" style="background:#f4f4ff" | <ref name = "Bubi">{{cite journal |vauthors=de Pablo R, García-Pacheco J, Vilches C, Moreno M, Sanz L, Rementería M, Puente S, Kreisler M | title = HLA class I and class II allele distribution in the Bubi population from the island of Bioko (Equatorial Guinea). | journal = Tissue Antigens | volume = 50 | issue = 6 | pages = 593–601 | year = 1997 | pmid = 9458112 | doi = 10.1111/j.1399-0039.1997.tb02917.x}}</ref>
|align="left" style="background:#f4f4ff;" | Bubi (Gabon)
|      ||       ||        || 12.5 
! style="background:#fafaff" |12.5
|-
|align="right" style="background:#f4f4ff" | <ref name = "Aka_Congo">{{cite journal |vauthors=Renquin J, Sanchez-Mazas A, Halle L, Rivalland S, Jaeger G, Mbayo K, Bianchi F, Kaplan C | title = HLA class II polymorphism in Aka Pygmies and Bantu Congolese and a reassessment of HLA-DRB1 African diversity. | journal = Tissue Antigens | volume = 58 | issue = 4 | pages = 211–22 | year = 2001 | pmid = 11782272 | doi = 10.1034/j.1399-0039.2001.580401.x}}</ref>
|align="left" style="background:#f4f4ff;" | Aka pygmy (Congo)
|      ||       ||        || 11.2 
! style="background:#fafaff" |11.2
|-
|align="right" style="background:#f4f4ff" | <ref name = "Algeria1">{{cite journal |vauthors=Arnaiz-Villena A, Benmamar D, Alvarez M, Diaz-Campos N, Varela P, Gomez-Casado E, Martinez-Laso J | title = HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques. | journal = Hum Immunol | volume = 43 | issue = 4 | pages = 259–68 | year = 1995 | pmid = 7499173 | doi = 10.1016/0198-8859(95)00024-X}}</ref>
|align="left" style="background:#f4f4ff;" |  Algeria
| 11.8   ||       || 35.3*    || 11.3 
! style="background:#fcfcff" |11.3
|-
|align="right" style="background:#f4f4ff" |<ref name = "IHWC11"/> 
|align="left" style="background:#f4f4ff;" |  Senegal
|      ||       ||        || 9.6 
! style="background:#fcfcff" | 9.6
|-
|align="right" style="background:#f4f4ff" | <ref name = "Amhara_OromoII">{{cite journal | doi = 10.1111/j.1399-0039.1998.tb02971.x |vauthors=Fort M, de Stefano G, Cambon-Thomsen A, Giraldo-Alvarez P, Dugoujon J, Ohayon E, Scano G, Abbal M | title = HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations. | journal = Tissue Antigens | volume = 51 | issue = 4 Pt 1 | pages = 327–36 | year = 1998 | pmid = 9583804}}</ref> 
|align="left" style="background:#f4f4ff;" | Amhara (Ethiopia)
| 6.5   || 20.9*  || 30.1*    || 7.7 
! style="background:#fcfcff" |7.7
|-
|align="right" style="background:#f4f4ff" | <ref name = "Aka_Congo"/> 
|align="left" style="background:#f4f4ff;" | Bantu (Congo)
| 6.5   || 17.1  || 35.3*    || 6.5 
! style="background:#fcfcff" |6.5
|-
|align="right" style="background:#f4f4ff" | <ref name = "IHWC11"/> 
|align="left" style="background:#f4f4ff"  |!Kung (Namibia)
| 1.9 ||   ||  11.9* ||  
! style="background:#fcfcff" | 1.9
|-
| style="background:#f4f4ff;color:#f4f4ff" | h 
| style="background:#f4f4ff" colspan="6" align="center" | * = Allele stated contains 2 or more alleles.
|}

DR3-DQ2  probably originated from Central or West Africa. DQ2.5cis haplotype is the second highest frequency haplotype in the Aka (N. Congo) and several other surrounding groups it is virtually absent in the !Kung.<ref name = "IHWC11">{{cite book  | last =  Kimiyoshi | first = Tsuji  | author2=Aizawa M |author3=Sasazuki T   | title = Proceedings of the Eleventh International Histocompatibility Workshop and Conference Held in Yokohoma, Japan, 6–13 November 1991  | publisher =  Oxford University Press  | year = 1992  |location = Oxford  | isbn = 0-19-262390-7}}</ref> DQ2.5 primarily spread to the northwest and appears to have spread late in global spread of anatomically modern humans. The !Kung and Austronesians<ref name = "IndonesianII">{{cite journal |vauthors=Mack S, Bugawan T, Moonsamy P, Erlich J, Trachtenberg E, Paik Y, Begovich A, Saha N, Beck H, Stoneking M, Erlich H | title = Evolution of Pacific/Asian populations inferred from HLA class II allele frequency distributions. | journal = Tissue Antigens | volume = 55 | issue = 5 | pages = 383–400 | year = 2000 | pmid = 10885559 | doi = 10.1034/j.1399-0039.2000.550501.x}}</ref> are reasonable marker populations earliest (eatward) spread out of Africa and those that spread rapidly, since the ancestors of the !Kung appear to have come from East Africa and share many Cw_B types in common with Austronesians and Northern Eurasians. DQ2.5 is at low frequencies in both of these populations, and it did not spread to Japan or the New World in pre-Columbian times. There is the possibility it spread to Arabia, but through stepwise expansion of small groups was lost from the DQ genetic repertoire.

DQ2.5 appears to be derived from DQ2.2 by gene recombination. One haplotype DQA1*0501:DQB1*0202 can be found in Africa suggesting DQB1*0201 evolved from DQB1*0202.
The regions of Africa where DQ2.5 is at its highest frequencies indicate potential sources for western European haplotypes (e.g. bedoin) but also indicate recent dispersion making precise evolution difficult to interpret. Other evidence for a west African origin/expansion is seen with the probable origin of DQA1*0501 from DQA1*0505, which is at relatively high frequencies in west-central Africa.

===Frequencies in Europe===
{| border="0" cellspacing="0" cellpadding="1" align="right" style="text-align:center; margin-right: 1em;  border:1px #bbffbb solid; background:#f8fff8; "
|+style="font-size:80%"|  '''B8, DR3 and DQ2.5 levels in Europeans''' (given as frequency in %)
|- style = "background:#dfffdf" 
!    !! align="left" width="80"|Reference
! B8  
!style = "font-size:90%" | DR17
!style = "font-size:90%" | DRB1
! Style="font-size:80%" |Haplo.  !! width="65" Style="font-size:80%" |Estimated
|- style = "background:#dfffdf" 
!   !! align="left"| Population  
|style = "font-size:80%" |(&A30B18)
|style = "font-size:90%" | (DR3) 
!0301!! Style="font-size:80%" | DR3DQ2!! DQ2.5
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/> 
| align="left" style="background:#f0fff0"  | Sardinian 
| (20.0)    || 25.7 ||           ||    21.9 
! style = "background:#fdfffd" | 22.0
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/> 
| align="left" style="background:#f0fff0"  | Basque (Spain)
| (15) ||       || 19.2   ||    21.9 
! style = "background:#fdfffd" | 22.0
|-
|align="right" style="background:#f0fff0" | <ref name = "W_Irish1">{{cite journal |vauthors=Michalski J, McCombs C, Arai T, Elston R, Cao T, McCarthy C, Stevens F | title = HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland. | journal = Tissue Antigens | volume = 47 | issue = 2 | pages = 127–33 | year = 1996 | pmid = 8851726 | doi = 10.1111/j.1399-0039.1996.tb02525.x}}</ref>
| align="left" style="background:#f0fff0"  | Western Irish <ref name = "W_Irish2">{{cite journal |vauthors=Savage D, Middleton D, Trainor F, Taylor A, Carson M, Stevens F, McCarthy C | title = HLA class II frequencies in celiac disease patients in the west of Ireland. | journal = Hum Immunol | volume = 34 | issue = 1 | pages = 47–52 | year = 1992 | pmid = 1356956 | doi = 10.1016/0198-8859(92)90084-Z}}</ref>
|      ||    ||      ||   20.8
! style = "background:#fdfffd" | 21.5
|-
|align="right" style="background:#f0fff0" | <ref name = "Irish">{{cite journal |vauthors=Finch T, Lawlor E, Borton M, Barnes C, McNamara S, O'Riordan J, McCann S, Darke C | title = Distribution of HLA-A, B and DR genes and haplotypes in the Irish population. | journal = Exp Clin Immunogenet | volume = 14 | issue = 4 | pages = 250–63 | year = 1997 | pmid = 9523161}}</ref> 
| align="left" style="background:#f0fff0"  | Irish<ref name = "N.IrishDRB1">{{cite journal |vauthors=Williams F, Meenagh A, Single R, McNally M, Kelly P, Nelson M, Meyer D, Lancaster A, Thomson G, Middleton D | title = High resolution HLA-DRB1 identification of a Caucasian population. | journal = Hum Immunol | volume = 65 | issue = 1 | pages = 66–77 | year = 2004 | pmid = 14700598 | doi = 10.1016/j.humimm.2003.10.004}}</ref><ref name = "N.IrishB">{{cite journal |vauthors=Middleton D, Williams F, Hamill M, Meenagh A | title = Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy. | journal = Hum Immunol | volume = 61 | issue = 12 | pages = 1285–97 | year = 2000 | pmid = 11163085 | doi = 10.1016/S0198-8859(00)00186-5}}</ref> 
| 17.7 || (17.4)   ||    || 
! style = "background:#fdfffd" | 17.0
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| align="left" style="background:#f0fff0"  | Swedish
| 16.0 ||    ||      || 15.9  
! 15.9
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Sanchez-Velasco P, Gomez-Casado E, Martinez-Laso J, Moscoso J, Zamora J, Lowy E, Silvera C, Cemborain A, Leyva-Cobián F, Arnaiz-Villena A | title = HLA alleles in isolated populations from North Spain: origin of the Basques and the ancient Iberians. | journal = Tissue Antigens | volume = 61 | issue = 5 | pages = 384–92 | year = 2003 | pmid = 12753657 | doi = 10.1034/j.1399-0039.2003.00041.x}}</ref> 
| align="left" style="background:#f0fff0"  | Arratia (Spain)
| (15.3) ||       || 17.3  ||    12.0
! style = "background:#fdfffd" | 12.0
|-
| align="right" style="background:#f0fff0" | <ref name = "Wales">{{cite journal |vauthors=Darke C, Guttridge M, Thompson J, McNamara S, Street J, Thomas M | title = HLA class I (A, B) and II (DR, DQ) gene and haplotype frequencies in blood donors from Wales. | journal = Exp Clin Immunogenet | volume = 15 | issue = 2 | pages = 69–83 | year = 1998 | pmid = 9691201 | doi = 10.1159/000019057| s2cid = 46788747 }}</ref>
| align="left" style="background:#f0fff0"  | Wales
| 16.5 ||    ||16.6|| 14.7  
! style = "background:#fdfffd" | 14.7
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Schipper R, Schreuder G, D'Amaro J, Oudshoorn M | title = HLA gene and haplotype frequencies in Dutch blood donors. | journal = Tissue Antigens | volume = 48 | issue = 5 | pages = 562–74 | year = 1996 | pmid = 8988539 | doi = 10.1111/j.1399-0039.1996.tb02670.x}}</ref>
| align="left" style="background:#f0fff0"  | Dutch
| 12.1 || (13.2) ||     || 14.4  
! style = "background:#fdfffd" | 13.2
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| 5.5 || (15.7) ||     || 14.2  
! style = "background:#fdfffd" | 14.2
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| align="left" style="background:#f0fff0"  | England
| 13.7 || (12.4) ||  ||
! style = "background:#fdfffd" | 12.4
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| align="left" style="background:#f0fff0"  | Yugoslavia
|  10.7  || (11.5) ||   || 12.0
! style = "background:#fdfffd" | 12.0
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| align="left" style="background:#f0fff0"  | Cornish
|  11.4  || (11.4) ||   || 11.4
! style = "background:#fdfffd" | 11.4
|-
|align="right" style="background:#f0fff0" | <ref name = "IHWC11"/>
| align="left" style="background:#f0fff0"  | Danish
|  8.9  || (11.3) ||    || 11.3
! style = "background:#fdfffd" | 11.3
|-
| align="left" style="background:#f0fff0"  | Swiss
| 10.3  || (11.6) || || 
! style = "background:#fdfffd" | 10.3
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Krokowski M, Bodalski J, Bratek A, Boitard C, Caillat-Zucman S | title = HLA class II allele and haplotype distribution in a population from central Poland. | journal = European Journal of Immunogenetics | volume = 25 | issue = 1 | pages = 5–9 | year = 1998 | pmid = 9587739 | doi = 10.1046/j.1365-2370.1998.00086.x}}</ref>
| align="left" style="background:#f0fff0"  | Poland<ref>{{cite journal |vauthors=Jungerman M, Sanchez-Mazas A, Fichna P, Ivanova R, Charron D, Hors J, Djoulah S | title = HLA class II DRB1, DQA1 and DQB1 polymorphisms in the Polish population from Wielkopolska. | journal = Tissue Antigens | volume = 49 | issue = 6 | pages = 624–8 | year = 1997 | pmid = 9234484 | doi = 10.1111/j.1399-0039.1997.tb02810.x| url = https://archive-ouverte.unige.ch/unige:17064 }}</ref> 
| 10.3  || (10.7) ||    || 10.7
! style = "background:#fdfffd" | 10.7
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Pedron B, Yakouben K, Adjaoud D, Auvrignon A, Landman J, Guerin V, Leverger G, Vilmer E, Sterkers G | title = Listing of common HLA alleles and haplotypes based on the study of 356 families residing in the Paris, France, area: implications for unrelated hematopoietic stem cell donor selection. | journal = Hum Immunol | volume = 66 | issue = 6 | pages = 721–31 | year = 2005 | pmid = 15993718 | doi = 10.1016/j.humimm.2005.02.007}}</ref> 
| align="left" style="background:#f0fff0"  | Paris
| (7.7)  || (10.1) ||  ||  9.7
! style = "background:#fdfffd" | 9.7
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "Israel_ArabII">{{cite journal |vauthors=Amar A, Kwon O, Motro U, Witt C, Bonne-Tamir B, Gabison R, Brautbar C | title = Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel. | journal = Hum Immunol | volume = 60 | issue = 8 | pages = 723–30 | year = 1999 | pmid = 10439318 | doi = 10.1016/S0198-8859(99)00043-9}}</ref> 
| align="left" style="background:#f0fff0"  | Arab Israeli
|   ||    ||  ||     9.6
! style = "background:#fdfffd" | 9.6
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name  = "Turks_Kurds">{{cite journal |vauthors=Arnaiz-Villena A, Karin M, Bendikuze N, Gomez-Casado E, Moscoso J, Silvera C, Oguz F, Sarper Diler A, De Pacho A, Allende L, Guillen J, Martinez Laso J | title = HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans. | journal = Tissue Antigens | volume = 57 | issue = 4 | pages = 308–17 | year = 2001 | pmid = 11380939 | doi = 10.1034/j.1399-0039.2001.057004308.x}}</ref> 
| align="left" style="background:#f0fff0"  | Turk
|   ||    || 9.6    || 9.2
! style = "background:#fdfffd" | 9.2
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "Finn_ABDR">{{cite journal |vauthors=Sirén M, Sareneva H, Lokki M, Koskimies S | title = Unique HLA antigen frequencies in the Finnish population. | journal = Tissue Antigens | volume = 48 | issue = 6 | pages = 703–7 | year = 1996 | pmid = 9008314 | doi = 10.1111/j.1399-0039.1996.tb02695.x}}</ref>
| align="left" style="background:#f0fff0"  | Finn<ref name = "Finn_RA">{{cite journal |vauthors=Laivoranta-Nyman S, Möttönen T, Hermann R, Tuokko J, Luukkainen R, Hakala M, Hannonen P, Korpela M, Yli-Kerttula U, Toivanen A, Ilonen J | title = HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis. | journal = Ann Rheum Dis | volume = 63 | issue = 11 | pages = 1406–12 | year = 2004 | pmid = 15479890 | doi = 10.1136/ard.2003.009969 | pmc = 1754800}}</ref>
| 8.9  || 6.0   ||     || 9.2
! style = "background:#fdfffd" | 9.0
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Evseeva I, Spurkland A, Thorsby E, Smerdel A, Tranebjaerg L, Boldyreva M, Groudakova E, Gouskova I, Alexeev L | title = HLA profile of three ethnic groups living in the North-Western region of Russia. | journal = Tissue Antigens | volume = 59 | issue = 1 | pages = 38–43 | year = 2002 | pmid = 11972877 | doi = 10.1034/j.1399-0039.2002.590107.x}}</ref> 
| align="left" style="background:#f0fff0"  | Russian
|    ||   || 9.5     || 9.0
! style = "background:#fdfffd" | 9.0
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "SvanI-II">{{cite journal |vauthors=Sánchez-Velasco P, Leyva-Cobián F | title = The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations. | journal = Tissue Antigens | volume = 58 | issue = 4 | pages = 223–33 | year = 2001 | pmid = 11782273 | doi = 10.1034/j.1399-0039.2001.580402.x}}</ref> 
| align="left" style="background:#f0fff0"  | Svanetian
| 6.8   || ||  8.7    ||
! style = "background:#fdfffd" | 8.7
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "Croatian">{{cite journal |vauthors=Grubić Z, Zunec R, Cecuk-Jelicić E, Kerhin-Brkljacić V, Kastelan A | title = Polymorphism of HLA-A, -B, -DRB1, -DQA1 and -DQB1 haplotypes in a Croatian population. | journal = European Journal of Immunogenetics | volume = 27 | issue = 1 | pages = 47–51 | year = 2000 | pmid = 10651851 | doi = 10.1046/j.1365-2370.2000.00193.x}}</ref>
| align="left" style="background:#f0fff0"  | Croatian
| 6.4   || ||  8.3    ||
! style = "background:#fdfffd" | 8.3
|-
|style="background:#f0fff0;color:#f0fff0" | <ref>{{cite journal |vauthors=Ivanova M, Rozemuller E, Tyufekchiev N, Michailova A, Tilanus M, Naumova E | title = HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations. | journal = Tissue Antigens | volume = 60 | issue = 6 | pages = 496–504 | year = 2002 | pmid = 12542743 | doi = 10.1034/j.1399-0039.2002.600605.x}}</ref> 
| align="left" style="background:#f0fff0"  | Bulgarian
| 18.2   || ||  8.2     ||
! style = "background:#fdfffd" | 8.0
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "greek_HLA3">{{cite journal |vauthors=Papassavas E, Spyropoulou-Vlachou M, Papassavas A, Schipper R, Doxiadis I, Stavropoulos-Giokas C | title = MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data. | journal = Hum Immunol | volume = 61 | issue = 6 | pages = 615–23 | year = 2000 | pmid = 10825590 | doi = 10.1016/S0198-8859(00)00115-4}}</ref> 
| align="left" style="background:#f0fff0"  | Greek
| 3.6   || ||  6.5   ||  6.3
! style = "background:#fdfffd" | 6.3
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "E_Bl_Sea_Turk">{{cite journal |vauthors=Uçar F, Ovali E, Pakdemir A, Alver A, Gök I, Karti S, Kalay E | title = HLA alleles and haplotypes in the east Black Sea Turkish population. | journal = Transplant Proc | volume = 36 | issue = 9 | pages = 2610–4 | year = 2004 | pmid = 15621102 | doi = 10.1016/j.transproceed.2004.10.020}}</ref> 
| align="left" style="background:#f0fff0"  | NE. Turk
| 3.4   || 5.6 ||         ||  
! style = "background:#fdfffd" | 5.4
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "MacedoniaII">{{cite journal |vauthors=Hristova-Dimceva A, Verduijn W, Schipper R, Schreuder G | title = HLA-DRB and -DQB1 polymorphism in the Macedonian population. | journal = Tissue Antigens | volume = 55 | issue = 1 | pages = 53–6 | year = 2000 | pmid = 10703609 | doi = 10.1034/j.1399-0039.2000.550109.x}}</ref> 
| align="left" style="background:#f0fff0"  | Macedonian
| 6.8   ||  ||  6.8    ||  5.0
! style = "background:#fdfffd" | 5.0
|-
|style="background:#f0fff0;color:#f0fff0" | <ref name = "Israel_1996">{{cite journal |vauthors=Martinez-Laso J, Gazit E, Gomez-Casado E, Morales P, Martinez-Quiles N, Alvarez M, Martin-Villa J, Fernandez V, Arnaiz-Villena A | title = HLA DR and DQ polymorphism in Ashkenazi and non-Ashkenazi Jews: comparison with other Mediterraneans. | journal = Tissue Antigens | volume = 47 | issue = 1 | pages = 63–71 | year = 1996 | pmid = 8929714 | doi = 10.1111/j.1399-0039.1996.tb02515.x}}</ref> 
| align="left" style="background:#f0fff0"  | non-Ashk Jew.
|    ||  ||  7.8       ||  4.4
! style = "background:#fdfffd" | 4.4
|-
|style="background:#f0fff0;color:#f0fff0" |  
|style="background:#f0fff0;color:#f0fff0" |  ||  colspan="7" align="center" |   
|}

In identifying DR3-DQ2 studies of DR3 and DQ8 frequencies, when DQ2.5 frequencies are not clear, are  helpful. DQ8 is helpful because of the strong linkage disequilibrium (LD) of the "super B8" haplotype. Unclear genetic information has come about because of false genotyping assumptions in older studies. DQB1*0201 may be available, but most often it is given incorrectly (DQB1*0201 = DQB1*0201 + DQB1*0202 + DQB1*0203). DQA1*0501 is often given incorrectly (DQB1*0501 = DQB1*0501 + DQB1*0505). These typing errors were not fully recognized until 2000.<ref name="pmid10777105">{{cite journal |vauthors=Pera C, Delfino L, Longo A, Pistillo MP, Ferrara GB | title = Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT) | journal = Tissue Antigens | volume = 55 | issue = 3 | pages = 275–9 | year = 2000 | pmid = 10777105 | doi =10.1034/j.1399-0039.2000.550313.x | url = https://zenodo.org/record/1231460 }}</ref> B8 frequencies are less useful in Southern and Eastern Europe, and there is no B allele that is in strong LD with DR3-DQ2. Therefore, as one moves east and southward B8 less predictive and DRB1*03 and DQB1*0201 (if DQB1*0202 is also given) must be relied upon.

European DR3-DQ2 is ancestrally derived from Africa, probably from Southwestern Europe or the Levant (in which DQ2.5 may have undergone negative, coeliac disease,  selection during the holocene). Since the last glacial maximum there appears to be two sources of DR3-DQ2. The first, propagating "super b8" is from Iberia into much of western and central Europe. The second, propagating [[Biology:A30-Cw5-B18-DR3-DQ2 (HLA Haplotype)|A30-B18-DR3-DQ2]], is from Africa into Sardinia, Iberia, France and Italy.

'''Anti-node in Western Europe'''. DR3-DQ2 was probably the predominant HLA haplotype in the early holocene Western and Central Europe, archaeological studies of France, particularly of the Paris Basin region indicate a cultural shift that occurs as a result of the neolithic revolution. In this region of France DR3-DQ2 specifically associated with super-B8 forms an anti-node of frequencies, whereas HLA types more common in Italy, Greece and the middle east are more common within this region of France. Other haplotypes indicate this introgression was significant over and the primary wheat farming regions of Europe.

'''Multiple Nodes'''. Because of the central location of the anti-node, the center of expansion of DR3-DQ2 with the recolonization of western Europe after the last glacial maximum has been obscured. However, the frequency is still high within the Basque of NE Spain, including some Super-B8 haplotype. The highest frequency of this node is in Western Ireland. Despite its high frequency Ireland is not likely the source of the haplotype in European, but a region that has been least disturbed by the negative selection of wheat culture and migrations. Much of Ireland was covered in glacial ice in the late paleolithic and few exploitable resources. Colonization started about 10500 years ago, whereas neolithization started about 6500 years ago and was dominated by cattle culture with some wheat and minor barley cultivation. The paleontology of Europe during the last glacial maximum suggests that the most likely places of origin are NE Iberia, Southern France and new ice-core evidence suggests that final spread northward probably occurred after [[Earth:Younger Dryas|Younger Dryas]].

===Frequencies in Asia===
{| border="0" cellspacing="0" cellpadding="1" align="left" style="text-align:center; margin-right: 1em;  border:1px #ffeebb solid; background:#fff7f8; "
|+ style="font-size:90%"|  DR3 and DQ2.5 levels in Asians (given as frequency in %)
|- style = "background:#ffe7d7" 
!    !! align="left" width="80"|Reference
!!style = "font-size:90%" | DR17
!style = "font-size:90%" | DRB1
! Style="font-size:80%" |Haplo.  !! width="65" Style="font-size:80%" |Estimated
|- style = "background:#ffe7d7"
!   !! align="left"| Population  
|style = "font-size:90%" | (DR3) 
!0301!! Style="font-size:80%" | DR3DQ2!! DQ2.5
|-
|align="right" style="background:#ffefe7" | <ref name = "Kazak">{{cite journal |vauthors=Mizuki M, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T, Ishihara M, Ota M, Geng Z, Geng L, Li G, Kimura M, Inoko H | title = Major histocompatibility complex class II alleles in Kazak and Han populations in the Silk Route of northwestern China. | journal = Tissue Antigens | volume = 50 | issue = 5 | pages = 527–34 | year = 1997 | pmid = 9389328 | doi = 10.1111/j.1399-0039.1997.tb02909.x}}</ref>
| align="left" style="background:#ffefe7" | Kazakh
| 13.1 ||  ||  
! style = "background:#fffaf7" | 13.1
|-
|align="right" style="background:#ffefe7" | <ref name = "Uygar">{{cite journal | doi = 10.1111/j.1399-0039.1998.tb03104.x |vauthors=Mizuki N, Ohno S, Ando H, Sato T, Imanishi T, Gojobori T, Ishihara M, Goto K, Ota M, Geng Z, Geng L, Li G, Inoko H | title = Major histocompatibility complex class II alleles in an Uygur population in the Silk Route of Northwest China. | journal = Tissue Antigens | volume = 51 | issue = 3 | pages = 287–92 | year = 1998 | pmid = 9550330}}</ref>
| align="left" style="background:#ffefe7" | Uygar (China) 
| 14.0 ||  || 12.6 
! style = "background:#fffaf7" | 12.6
|-
|align="right" style="background:#ffefe7" | <ref name = "khalkha">{{cite journal |vauthors=Machulla H, Batnasan D, Steinborn F, Uyar F, Saruhan-Direskeneli G, Oguz F, Carin M, Dorak M | title = Genetic affinities among Mongol ethnic groups and their relationship to Turks. | journal = Tissue Antigens | volume = 61 | issue = 4 | pages = 292–9 | year = 2003 | pmid = 12753667 | doi = 10.1034/j.1399-0039.2003.00043.x}}</ref>
| align="left" style="background:#ffefe7" |  Tsaatan (Mongolia) 
| 12.5 ||  ||  
! style = "background:#fffaf7" | 12.5
|-
|align="right" style="background:#ffefe7" | <ref name = "khalkha"/>
| align="left" style="background:#ffefe7" |  Khalka (Mongolia) <ref name = "Khalkha2">{{cite journal |vauthors=Chimge N, Tanaka H, Kashiwase K, Ayush D, Tokunaga K, Saji H, Akaza T, Batsuuri J, Juji T | title = The HLA system in the population of Mongolia. | journal = Tissue Antigens | volume = 49 | issue = 5 | pages = 477–83 | year = 1997 | pmid = 9174140 | doi = 10.1111/j.1399-0039.1997.tb02782.x}}</ref>
| 9.0 ||  || 11.5 
! style = "background:#fffaf7" | 11.5
|-
|align="right" style="background:#ffefe7" | <ref name = "IHC12">{{cite journal | title = 12th International Histocompatibility Conference. Genetic diversity of HLA: functional and medical implications. Paris, France, June 9–12, 1996. Abstracts. | journal = Hum Immunol | volume = 47 | issue = 1–2 | pages = 1–184 | year = 1996| pmid = 8909580}}</ref>
| align="left" style="background:#ffefe7" |  Australia (New South Wales) 
|   ||  || 11.4 
! style = "background:#fffaf7" | 11.4
|-
|align="right" style="background:#ffefe7" | <ref name = "Iran">{{cite journal |vauthors=Amirzargar A, Mytilineos J, Farjadian S, Doroudchi M, Scherer S, Opelz G, Ghaderi A | title = Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. | journal = Hum Immunol | volume = 62 | issue = 11 | pages = 1234–8 | year = 2001 | pmid = 11704285 | doi = 10.1016/S0198-8859(01)00320-2}}</ref>
| align="left" style="background:#ffefe7" |  Iranian 
| 10.0  ||  || 10.0 
! style = "background:#fffaf7" | 10.0
|-
|align="right" style="background:#ffefe7" | <sup>[http://www.allelefrequencies.net/test/searchAllelePart3-1.asp?Population=Vietnam%20HoaBinh%20Muong] {{Webarchive|url=https://web.archive.org/web/20070927005030/http://www.allelefrequencies.net/test/searchAllelePart3-1.asp?Population=Vietnam%20HoaBinh%20Muong |date=2007-09-27 }}</sup> 
| align="left" style="background:#ffefe7" |  Muong (Viet Nam)
| 12.7  ||  || 9.8 
! style = "background:#fffaf7" | 9.8
|-
|align="right" style="background:#ffefe7" | <ref name = "khalkha"/>
| align="left" style="background:#ffefe7" |  Oold (Mongolia) 
|   ||  || 8.7 
! style = "background:#fffaf7" | 8.7
|-
|align="right" style="background:#ffefe7" | <ref name = "Jing">{{cite journal |vauthors=Lin J, Liu Z, Lv F, Fu Y, Fan X, Li S, Lu J, Liu X, Xu A | title = Molecular analyses of HLA-DRB1, -DPB1, and -DQB1 in Jing ethnic minority of Southwest China. | journal = Hum Immunol | volume = 64 | issue = 8 | pages = 830–4 | year = 2003 | pmid = 12878363 | doi = 10.1016/S0198-8859(03)00128-9}}</ref>
| align="left" style="background:#ffefe7" |  Jing (China)
|   ||  || 8.1 
! style = "background:#fffaf7" | 8.1
|-
|align="right" style="background:#ffefe7" | <ref name = "Uygar"/>
| align="left" style="background:#ffefe7" |  N.W. Han (China)
| 7.6  ||  || 7.6
! style = "background:#fffaf7" | 7.6
|-
|align="right" style="background:#ffefe7" | <ref name = "Siberia8pop">{{cite journal |vauthors=Uinuk-Ool T, Takezaki N, Sukernik R, Nagl S, Klein J | title = Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies. | journal = Hum Genet | volume = 110 | issue = 3 | pages = 209–26 | year = 2002 | pmid = 11935333 | doi = 10.1007/s00439-001-0668-0| s2cid = 20940785 }}</ref>
| align="left" style="background:#ffefe7" |  Mansi (Russia)
|  || 7.4  || 7.4
! style = "background:#fffaf7" | 7.4
|-
|align="right" style="background:#ffefe7" | <ref name = "N_indiaII">{{cite journal |vauthors=Rani R, Fernandez-Viña M, Stastny P | title = Associations between HLA class II alleles in a North Indian population. | journal = Tissue Antigens | volume = 52 | issue = 1 | pages = 37–43 | year = 1998 | pmid = 9714472 | doi = 10.1111/j.1399-0039.1998.tb03021.x}}</ref>
| align="left" style="background:#ffefe7" | N.India
| 7.4  ||  || 7.4
! style = "background:#fffaf7" | 7.4
|-
|align="right" style="background:#ffefe7" | <ref name ="ShirazYadz">{{cite journal |vauthors=Farjadian S, Moqadam F, Ghaderi A | title = HLA class II gene polymorphism in Parsees and Zoroastrians of Iran. | journal = International Journal of Immunogenetics | volume = 33 | issue = 3 | pages = 185–91 | year = 2006 | pmid = 16712649 | doi = 10.1111/j.1744-313X.2006.00594.x| s2cid = 12667253 }}</ref>
| align="left" style="background:#ffefe7" | Iran (Yadz)
| 5.4  ||  || 5.4
! style = "background:#fffaf7" | 5.4
|-
|align="right" style="background:#ffefe7" | <ref name = "VietnamII">{{cite journal |vauthors=Vu-Trieu A, Djoulah S, Tran-Thi C, Ngyuyen-Thanh T, Le Monnier De Gouville I, Hors J, Sanchez-Mazas A | title = HLA-DR and -DQB1 DNA polymorphisms in a Vietnamese Kinh population from Hanoi. | journal = European Journal of Immunogenetics | volume = 24 | issue = 5 | pages = 345–56 | year = 1997 | pmid = 9442802 | doi = 10.1046/j.1365-2370.1997.d01-107.x}}</ref>
| align="left" style="background:#ffefe7" | Hanoi (Viet Nam)
| 4.4  ||  || 4.0
! style = "background:#fffaf7" | 4.0
|-
|align="right" style="background:#ffefe7" | <ref name = "Siberia8pop"/>
| align="left" style="background:#ffefe7" | Buryat (Siberia)
|    || 4.0 || 4.0
! style = "background:#fffaf7" | 4.0
|-
|align="right" style="background:#ffefe7" | <ref name = "ShandongII">{{cite journal |vauthors=Zhou L, Lin B, Xie Y, Liu Z, Yan W, Xu A | title = Polymorphism of human leukocyte antigen-DRB1, -DQB1, and -DPB1 genes of Shandong Han population in China. | journal = Tissue Antigens | volume = 66 | issue = 1 | pages = 37–43 | year = 2005 | pmid = 15982255 | doi = 10.1111/j.1399-0039.2005.00418.x}}</ref>
| align="left" style="background:#ffefe7" | Shandong (China)
|    ||  || 3.6
! style = "background:#fffaf7" | 3.6
|-
|align="right" style="background:#ffefe7" | <ref name = "Korea485">{{cite journal |vauthors=Lee K, Oh D, Lee C, Yang S | title = Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. | journal = Tissue Antigens | volume = 65 | issue = 5 | pages = 437–47 | year = 2005 | pmid = 15853898 | doi = 10.1111/j.1399-0039.2005.00386.x}}</ref>
| align="left" style="background:#ffefe7" | Korean
|    ||2.9 || 2.9
! style = "background:#fffaf7" | 2.9
|-
|align="right" style="background:#ffefe7" | <ref name = "IndonesianII"/>
| align="left" style="background:#ffefe7" | Nusa Ten. (Indonesia)
|  || 2.4 || 2.4 
! style = "background:#fffaf7" | 2.4
|-
|align="right" style="background:#ffefe7" | <ref name = "Siberia8pop"/>
| align="left" style="background:#ffefe7" | Ulchi
| || 1.4  || 1.4
! style = "background:#fffaf7" | 1.4
|-
|align="right" style="background:#ffefe7" | <ref name = "Okinawa">{{cite journal |vauthors=Hatta Y, Ohashi J, Imanishi T, Kamiyama H, Iha M, Simabukuro T, Ogawa A, Tanaka H, Akaza T, Gojobori T, Juji T, Tokunaga K | title = HLA genes and haplotypes in Ryūkyūans suggest recent gene flow to the Okinawa Islands. | journal = Hum Biol| volume = 71 | issue = 3 | pages = 353–65 | year = 1999 | pmid = 10380372}}</ref>
| align="left" style="background:#ffefe7" | Ryūkyū (Japan)
| 0.0 ||  || 0.0
! style = "background:#fffaf7" | 0.0
|-
|align="right" style="background:#ffefe7" | <ref name = "JapaneseI-II">{{cite journal |vauthors=Saito S, Ota S, Yamada E, Inoko H, Ota M | title = Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population. | journal = Tissue Antigens | volume = 56 | issue = 6 | pages = 522–9 | year = 2000 | pmid = 11169242 | doi = 10.1034/j.1399-0039.2000.560606.x| doi-access = free }}</ref>
| align="left" style="background:#ffefe7" | Japanese
|  || 0.7 || 0.3
! style = "background:#fffaf7" | 0.3
|-
|align="right" style="background:#ffefe7" | <ref name = "Ainu2">{{cite journal |vauthors=Bannai M, Tokunaga K, Imanishi T, Harihara S, Fujisawa K, Juji T, Omoto K | title = HLA class II alleles in Ainu living in Hidaka District, Hokkaidō, northern Japan. | journal = Am J Phys Anthropol | volume = 101 | issue = 1 | pages = 1–9 | year = 1996 | pmid = 8876810 | doi = 10.1002/(SICI)1096-8644(199609)101:1<1::AID-AJPA1>3.0.CO;2-Z}}</ref>
| align="left" style="background:#ffefe7" | Ainu(Japan)
|  || 0.0 || 0.0
! style = "background:#fffaf7" | 0.0
|-
|align="right" style="background:#ffefe7" | <ref name = "Nganasan-Ket">{{cite journal |vauthors=Uinuk-Ool T, Takezaki N, Derbeneva O, Volodko N, Sukernik R | title = Variation of HLA class II genes in the Nganasan and Ket, two aboriginal Siberian populations. | journal = European Journal of Immunogenetics | volume = 31 | issue = 1 | pages = 43–51 | year = 2004 | pmid = 15009181 | doi = 10.1111/j.1365-2370.2004.00443.x}}</ref>
| align="left" style="background:#ffefe7" | ket(Russia)
| 0.0 ||  || 0.0
! style = "background:#fffaf7" | 0.0
|-
|align="right" style="background:#ffefe7" | <ref name = "Nganasan-Ket"/>
| align="left" style="background:#ffefe7" | Ngasan(Siberia)
| 0.0 ||  || 0.0
! style = "background:#fffaf7" | 0.0
|-
|align="right" style="background:#ffefe7" | <ref name = "Siberia8pop"/>
| align="left" style="background:#ffefe7" | Negidal(Siberia)
|  || 0.0 || 0.0
! style = "background:#fffaf7" | 0.0
|-
|align="right" style="background:#ffefe7" | <ref name = "IndonesianII"/>
| align="left" style="background:#ffefe7" | Molacca(Indonesia)
|  || 0.0 || 0.0
! style = "background:#fffaf7" | 0.0
|-
|}

Based on frequencies in Central and East Asia, DR3_DQ2 appears to have spread eastward recently. Of particular interest to the West African/Central Asian comparison, not only is DQ3-DQ2.5 elevated in both places, but a linked HLA A-B haplotype, A33-B58,<ref name = "IHWC11"/> is found in West Africans and both the A33 and B58 alleles show more allelic and haplotype diversity in West Africa. This similarity would be remarkable if this haplotype came with migrations 50,000 to 130,000 years ago, since considerable equilibration and long range migrations are expected  over this time frame. Ironically, there is no convincing route of travel between West Africa and Central Asia suggested by gene frequencies in the peoples between the two.  This recent migration hypothesis is supported by HLA-A36 which shows a similar African/Central Asian bimodal distribution. One population that might have been related to this migration are non-caucasians of northern Africa.

DR3-DQ2 is notably higher in W. Mongolia, Kazakhstan and W. China. One eastern haplotype is "A33-B58" and has some punctuated distribution in Western Europe at relatively low levels, and is also in extreme disequilibrium where it is found, elsewhere. In Thailand it is elevated, particularly in the Thai Chinese, but in the south and most parts of Indonesia its frequency is zero. Elevated DR3-DQ2 levels in the Muong suggest a similar North to South spread.

DR3-DQ2 presence in the Koreans and lack thereof in the Japanese suggest a recent spread into Western Pacific Rim of Asia. By HLA, Y chromosome, or mitochondrial DNA the Japanese are about 60-85% of post-Jōmon period Korean origin, and the level of DR3-DQ2 in Japanese is about 1/10 that of Koreans suggesting that DR3-DQ2 did not spread in the Yayoi and that it spread recently with Mongol spread in Eastern Asia, it is rare both east and south of China (except in regions with strong historic migrations of Chinese), rare in Indigenous Austronesians, and isolated Indigeonous American groups.

===The importance of the estimates===
Currently, in assessing diseases like Coeliac disease a definite diagnosis is often not possible and statistical considerations are relied upon. The knowledge of frequencies in populations, particularly among ancestors of immigrants can aid patient and physician as to the potential risks.<ref name="pmid17785484">{{cite journal  |vauthors=Hadithi M, von Blomberg BM, Crusius JB, etal | title = Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease | journal = Annals of Internal Medicine | volume = 147 | issue = 5 | pages = 294–302 | year = 2007 | pmid = 17785484 | doi = 10.7326/0003-4819-147-5-200709040-00003| s2cid = 24275278 }}</ref> An example, one publication states that the western regions of Ireland have the highest coeliac disease rate in the world.<ref>{{cite journal |vauthors=Zhong F, McCombs C, Olson J, Elston R, Stevens F, McCarthy C, Michalski J | title = An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland. | journal = Nat Genet | volume = 14 | issue = 3 | pages = 329–33 | year = 1996 | pmid = 8896565 | doi = 10.1038/ng1196-329| s2cid = 23667150 }}</ref> Plotting the frequency of DQ2.5 from any part of Western Europe to the Irish one sees the frequency gradient progressing toward the north and west of Ireland; therefore, a high rate of coeliac disease is not unexpected in Western Ireland. People with many common ancestors from Ireland share similar risks of disease.

In the case of juvenile diabetes a clear distinction of DR3-DQ2 from DR7-DQ2 is necessary
because both DR3 and DQ2 confer risk of disease. And DR3-DQ2/DR4-DQ8 individuals who have type 1 diabetes (late onset) are often mistaken for type-2 diabetes.

==Associated Diseases==
DR3-DQ2 is associated with probably the greatest frequency of '''autoimmune''' occurrence relative to any other haplotype. The DQA1*0501:DQB1*0201 (DQ2.5) locus confers susceptibility to Gluten Sensitive Enteropathy (GSE)and ([[Medicine:Diabetes mellitus type 1|Type 1 Diabetes]]) but has also been linked to other rarer autoimmune diseases like [[Medicine:Myasthenia gravis|myasthenia gravis]].


===Type 1 diabetes===
In type 1 diabetes both DR3 and DQ2 appear to play a role.

*DR3-DQ2.5 can be established to other genes like TNF-305A (TNF2) which may also increase the risk of autoimmune disease in both Coeliac Disease and Type 1 diabetes. In systemic lupus erythematosus (SLE) patients HLA DR3-DQ2.5-C4AQ0, which was strongly associated with SLE ([[Odds ratio|odds ratio]] [OR] 2.8, 95% CI 1.7-4.5).<ref>{{cite journal |vauthors=Jönsen A, Bengtsson A, Sturfelt G, Truedsson L | title = Analysis of HLA DR, HLA DQ, C4A, FcgammaRIIa, FcgammaRIIIa, MBL, and IL-1Ra allelic variants in Caucasian systemic lupus erythematosus patients suggests an effect of the combined FcgammaRIIa R/R and IL-1Ra 2/2 genotypes on disease susceptibility. | journal = Arthritis Research & Therapy | volume = 6 | issue = 6 | pages = R557–62 | year = 2004 | pmid = 15535834 | doi = 10.1186/ar1224 | pmc = 1064866 | doi-access = free }}</ref>
* A more recent paper shows that Inositol triphosphate receptor 3 gene which is ~ 1 million base pairs from DQ2.5 is also associated with Type 1 diabetes.<ref>{{cite journal |vauthors=Roach J, Deutsch K, Li S, Siegel A, Bekris L, Einhaus D, Sheridan C, Glusman G, Hood L, Lernmark A, Janer M | title = Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden. | journal = American Journal of Human Genetics | volume = 79 | issue = 4 | pages = 614–27 | year = 2006 | pmid = 16960798 | doi = 10.1086/507876 | pmc = 1592562}}</ref>

===Sarcoidosis===
A relationship between HLA and [[Medicine:Sarcoidosis|sarcoidosis]] has been known for 30+ years.<ref name="pmid15003948">{{cite journal |vauthors=Rybicki BA, Iannuzzi MC |title=Sarcoidosis and human leukocyte antigen class I and II genes: it takes two to tango? |journal=Am. J. Respir. Crit. Care Med. |volume=169 |issue=6 |pages=665–6 |date=March 2004 |pmid=15003948 |doi=10.1164/rccm.2401005 }}</ref> However, the association is weak and has not been reproducible in all studies.  A common serologically defined haplotype in Europeans is [[Biology:HLA A1-B8-DR3-DQ2|HLA A1-B8-DR3-DQ2]].5 (see above). In non-persistent sarcoidosis this haplotype was found to be increased in sarcoidosis, and further study eliminated risk contributed by A1-Cw7-B8 indicating DR3-DQ2 haplotype contains risk of disease (OR = 11.8)<ref name="pmid14656748">{{cite journal |vauthors=Grunewald J, Eklund A, Olerup O |title=Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients |journal=Am. J. Respir. Crit. Care Med. |volume=169 |issue=6 |pages=696–702 |date=March 2004 |pmid=14656748 |doi=10.1164/rccm.200303-459OC |s2cid=16435273 }}</ref>

===Extended linkage===
* DQ2.5 is also linked to the IgA-less phenotype which may or may not increase susceptibility to diseases.<ref>{{cite journal |vauthors=Schaffer F, Palermos J, Zhu Z, Barger B, Cooper M, Volanakis J | title = Individuals with IgA deficiency and common variable immunodeficiency share polymorphisms of major histocompatibility complex class III genes. | journal = Proc Natl Acad Sci USA | volume = 86 | issue = 20 | pages = 8015–9 | year = 1989 | pmid = 2573059 | doi = 10.1073/pnas.86.20.8015 | pmc = 298204| bibcode = 1989PNAS...86.8015S | doi-access = free }}</ref><ref>{{cite journal |vauthors=Klemola T, Savilahti E, Koskimies S, Pelkonen P | title = HLA antigens in IgA deficient paediatric patients. | journal = Tissue Antigens | volume = 32 | issue = 4 | pages = 218–23 | year = 1988 | pmid = 3217938 | doi = 10.1111/j.1399-0039.1988.tb01659.x}}</ref> This imposes a problem for understanding autoimmunity in DQ2.5, since many genes linked to disease with partial contributions are some degree of disequilibration with DQ2.5 loci and thus DQ2.5 masks genetic association via it positive association with some many diseases.

==References==
{{reflist|2}}

==External links==
'''Coeliac Disease'''
* [http://www.coeliac.co.uk/ Coeliac UK] {{Webarchive|url=https://web.archive.org/web/20060527003650/http://www.coeliac.co.uk/ |date=2006-05-27 }} (charity)
* [http://www.celiac.org/ The Celiac Disease Foundation] (U.S.)
* [https://web.archive.org/web/20090720193635/http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/ National Digestive Diseases Clearinghouse] - page on coeliac disease
* [http://www.celiacawareness.org National Foundation for Celiac Awareness] (U.S.)
* [http://www.celiaccenter.org/ University of Maryland Center for Celiac Research]

'''Type 1 Diabetes'''
*[http://www.childrenwithdiabetes.com/ Children with Diabetes]
*[https://web.archive.org/web/20091030082136/https://www.diabetes.org/type-1-diabetes.jsp Type 1 Diabetes] at the American Diabetes Association

{{DEFAULTSORT:Hla Dr3-Dq2}}
[[Category:HLA-DQ haplotypes|2]]
[[Category:HLA-DR haplotypes|3]]
[[Category:Human MHC haplogroups]]

{{Sourceattribution|HLA DR3-DQ2}}