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major histocompatibility complex, class II, DQ4
Haplotype(s) DQA1*0303:DQB1*0401, DQA1*0303:DQB1*0402, DQA1*0401:DQB1*0402
alpha 1 *0303 or *0401
Symbol(s) HLA-DQA1
Entrez 3117
OMIM 146880
beta 1 *0401 or *0402
Symbol(s) HLA-DQB1
Entrez 3119
OMIM 604305
Shared data
Locus chr.6 6p21.31

HLA DQ4 is an HLA-DQ serotype grouping based on antibody recognition of the HLA DQ beta chain. It is synonymous with the HLA-DQB1*04 allelegroup. This group is composed of two similar beta chains. HLA DQB1*0401, and HLA DQB1*0402. These beta chains are linked to certain alpha chain genes (alleles) such as DQB1*0302, *0303, and *0401.



  • DQ4
    • *0401 DQ4 [71%] DQ3 [10%] N = 176
    • *0402 DQ4 [86%] DQ3 [2%] blank [7%] N = 1085

derived from IMGT/HLA


DQA1*0303:DQB1*0401 is linked to DRB1*0405 and is commmon on the west pacific rim, from Indonesia to Japan and inland areas of Eastern Asia. In Japan it confers susceptibility to type 1 diabetes.


DQA1*0303:DQB1*0402 is primarily found in Northeastern Asia and the west pacific rim. It is similar to DQA1*0303:DQB1*0402.

DQB1*0401:DQB1*0402 has a trimodal global distribution. The highest frequencies are found in the highland reagions of the new world, peaking in NW Mexico and in the Andes. It is also found at high levels in Namibia and Botswana. Between these two population it is moderatedly high in the Ainu of northern Japan.

DQ4 and Disease

DQ4 is associated with:

  • juvenile diabetic retinopathy [1][2]

The DR8-DQ4 haplotype is associated with

  • papillary thyroid carcinomas[3]
  • juvenile idiopathic arthritis[4] via DR8 allele [5],
  • chronic chlamydia infection[6],
  • possibly pemphigus [7]

DR4-DQ4(DRB1*0405:DQB1*0401) is associated with:

The DQA1*0303:DQB1*04 haplotype is associated with:

Other diseases mentioned are high altitude pulmonary edema, Vogt-Koyanagi-Harada syndrome (DRB1*0405, see above table for Japanese), HIV resistance in the US, and haemophilia A(anti-FVIII inhibitor response).

DQ4 distribution

20 of the most common DR-DQ haplotypes in Japanese
Serotype haplotype B1 A1 B1 %[13] rank
DQ4 DR4-DQ4 0405 0303 0401 14. 3 ²
0410 0303 0402 1. 9 11
DR8-DQ4 0802 0401 0402 1. 3 15
DQ5 DR1-DQ5 0101 0101 0501 6. 4 5
DR14-DQ5 1401 0104 0502 1. 1 17
1401 0104 0503 0. 8 18
1405 0104 0503 1. 6 13
DQ6 DR8-DQ6 0803 0103 0601 9. 3 4
DR13-DQ6 1302 0102 0604 6. 0 6
DR15-DQ6 1502 0103 0601 12. 9 ³
1501 0102 0602 6. 0 7
DQ7 DR11-DQ7 1101 0505 0301 1. 8 12
DR12-DQ7 1201 0505 0301 2. 7 9
1202 0601 0301 1. 3 15
DR14-DQ7 1403 0503 0301 1. 4 14
DQ8 DR4-DQ8 0403 0301 0302 1. 9 10
0406 0301 0302 3. 4 8
DR8-DQ8 0802 0401 0302 0. 7 19
DQ9 DR9-DQ9 0901 0302 0303 16. 0 1

The table to the left shows the values of Japanese[13](values converted from phenotype frequencies to haplotype frequencies for sake of consistency) DR-DQ types. This table is presented here because of the diversity of DQ4 types in the Japanese population not seen elsewhere. DQ4 is typically rare most of the world but where it appears more frequently is something of interest. The node of DQ4 is with the DQA1*0401:DQB1*0402 (DQ4.24 for this page) haplotype in Northwestern Mexico and the highland region of western South America reaching 40% haplotype frequencies in that area. Outside of the Indigenous American population DQ4.24 is elevated at 10% in the Ainu of Hokkaidō, Japan. There are a number of other A-B haplotypes that suggest a connection between the Ainu and the Meso-American and Andean populations as well as Lakota Souix all have DQ4 levels higher than the Ainu. The linkage of DQ4 in Asia appears to be heaviest with DR8 (DR*0801, DR*0802, DR*0804) for DQ4.24 and the frequency is elevated from the Ryukyu Islands to Okhotsk, Ulchi, Negidal, Tofalar at approximately 10% falling off in the Mansi at 4% and punctate levels in between. Haplotype diversity of DQB1*0402 appears to be centered around the Amur River/Japanese Island Chain, and diversity of DQB1*0401 very roughly follows a similar pattern. DQ4.24 is also high in the Swedes however this may be due to east to west gene flow tracable at other HLA loci.

Since DQA1*0401:DQB1*0402 is found in the !Kung, one reasonably assumes it evolved in Africa and migrated with one of several potential waves, probably the earliest. Tracing the migration route is excessively difficult, but it appears that a possible second node of expansion in Central Asia and not the West Pacific Rim/Austro-Indic route postulated as the early human distribution. The most common haplotypes in the !Kung (for example Cw-B) that also appear in Eurasia appear to have been associated with the earliest migration, and is suggestive of a coastal migration; however the relatively high frequencies in the Ainu[14] and Amur basin[15] suggest a migration through the Transbaikal that is consistent with archaeology from about 18 kya. One expects with such a route that Korean would be higher than Japanese and Japanese higher the Ryukuans still higher than Taiwan aboriginals. From the west gene frequencies in the Levant and Black Sea region are at 'diffusive' levels whereas there are pockets of increased frequency in the Zoroastrians of Yadz region (DQA1*0401 and DQB1*0402). Thus the DR8-DQ4.24 haplotype is probably one of western origin.

The DR4-DQA1*0303:DQB1*040X can be found at high frequencies in PNG highland groups [16] but not DQ4.24. The DR*0405 and DR*410 are found specifically associated with these DQ types and there is some haplotype diversity. So that it appears the presence of the DQA1*03:DQB1*04 is of West Pacific Rim origins in Japanese and proximal Siberians, but unfortunately there is no current typing of these haplotypes in the Taiwan aboriginal population. The presence in Indonesia may be the result of retrograde gene flow that can be established by other HLA types as well as mtDNA.


  1. ^ Mimura T, Funatsu H, Uchigata Y, Kitano S, Noma H, Shimizu E, Konno Y, Amano S, Araie M, Yoshino O, Iwamoto Y, Hori S (2003). "Relationship between human leukocyte antigen status and proliferative diabetic retinopathy in patients with younger-onset type 1 diabetes mellitus.". Am J Ophthalmol 135 (6): 844-8. PMID 12788125.
  2. ^ Mimura T, Funatsu H, Uchigata Y, Kitano S, Shimizu E, Amano S, Yamagami S, Noma H, Araie M, Hori S (2005). "Glutamic acid decarboxylase autoantibody prevalence and association with HLA genotype in patients with younger-onset type 1 diabetes and proliferative diabetic retinopathy.". Ophthalmology 112 (11): 1904-9. PMID 16157380.
  3. ^ Porto T, Coelho I, Boavida J, Pereira C, Nunes J, Mendonça D, Martins B, Sobrinho L, Leite V (2006). "Association of HLA DQ4-DR8 haplotype with papillary thyroid carcinomas.". Clin Endocrinol (Oxf) 64 (2): 179-83. PMID 16430717.
  4. ^ Smerdel A, Lie B, Finholt C, Ploski R, Førre Ø, Undlien D, Thorsby E (2003). "An additional susceptibility gene for juvenile idiopathic arthritis in the HLA class I region on several DR-DQ haplotypes.". Tissue Antigens 61 (1): 80-4. PMID 12622778.
  5. ^ Smerdel A, Ploski R, Flatø B, Musiej-Nowakowska E, Thorsby E, Førre Ø (2002). "Juvenile idiopathic arthritis (JIA) is primarily associated with HLA-DR8 but not DQ4 on the DR8-DQ4 haplotype.". Ann Rheum Dis 61 (4): 354-7. PMID 11874841.
  6. ^ Betsou F, Borrego M, Guillaume N, Catry M, Romão S, Machado-Caetano J, Sueur J, Mention J, Faille N, Orfila J (2003). "Cross-reactivity between Chlamydia trachomatis heat shock protein 10 and early pregnancy factor.". Clin Diagn Lab Immunol 10 (3): 446-50. PMID 12738647.
  7. ^ Birol A, Anadolu R, Tutkak H, Gürgey E (2002). "HLA-class 1 and class 2 antigens in Turkish patients with pemphigus.". Int J Dermatol 41 (2): 79-83. PMID 11982641.
  8. ^ Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, Nakayama K, Tokutake Y, Katsuyama Y, Saito S, Hasebe O, Kiyosawa K (2002). "HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population.". Gastroenterology 122 (5): 1264-9. PMID 11984513.
  9. ^ Kikuoka N, Sugihara S, Yanagawa T, Ikezaki A, Kim H, Matsuoka H, Kobayashi Y, Wataki K, Konda S, Sato H, Miyamoto S, Sasaki N, Sakamaki T, Niimi H, Murata M (2001). "Cytotoxic T lymphocyte antigen 4 gene polymorphism confers susceptibility to type 1 diabetes in Japanese children: analysis of association with HLA genotypes and autoantibodies.". Clin Endocrinol (Oxf) 55 (5): 597-603. PMID 11894970.
  10. ^ Tsuchiya K, Kimura A, Kondo M, Nishimura Y, Sasazuki T (2001). "Combination of HLA-A and HLA class II alleles controls the susceptibility to rheumatoid arthritis.". Tissue Antigens 58 (6): 395-401. PMID 11929590.
  11. ^ Matake H, Okabe N, Naito S, Yao T (1992). "An HLA study on 149 Japanese patients with Crohn's disease.". Gastroenterol Jpn 27 (4): 496-501. PMID 1526431.
  12. ^ Nakajima A, Matsuhashi N, Kodama T, Yazaki Y, Takazoe M, Kimura A (1995). "HLA-linked susceptibility and resistance genes in Crohn's disease.". Gastroenterology 109 (5): 1462-7. PMID 7557126.
  13. ^ a b Tanaka T, Ohmori M, Yasunaga S, Ohshima K, Kikuchi M, and Sasazuki T. (1999). "DNA typing of HLA class II genes (HLA-DR, -DQ and -DP) in Japanese patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease).". Tissue Antigens 54 (3): 246-253. PMID 10519361.
  14. ^ Bannai M, Tokunaga K, Imanishi T, Harihara S, Fujisawa K, Juji T, and Omoto K. (1996). "HLA class II alleles in Ainu living in Hidaka District, Hokkaidō, northern Japan.". Am J Phys Anthropol 101 (1): 1-9. PMID 8876810.
  15. ^ Uinuk-Ool TS, Takezaki N, Sukernik RI, Nagl S, Klein J. (2002). "Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies.". Human Genetics 110 (3): 209-226. PMID 11935333.
  16. ^ Gao X, Bhatia K, Trent RJ, and Serjeantson SW. (1992). "HLA-DR, DQ nucleotide sequence polymorphisms in five Melanesian populations.". Tissue Antigens 40 (1): 31-37. PMID 1440559.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "HLA-DQ4". A list of authors is available in Wikipedia.
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