HLA-DQ6
Illustration of HLA-DQ with bound peptide
Polymer typeMHC Class II, DQ cell surface antigen
Cis-haplotype Haplotype
isoform subtype DQA1 DQB1
DQ α1.3β6.1 DQ6.1 *0103 *0601
DQ α1.2β6.2 DQ6.2 *0102 *0602
DQ α1.3β6.3 DQ6.3 *0103 *0603
DQ α1.2β6.4 DQ6.4 *0102 *0604
Rare haplotypes
Cis-haplotype Haplotype
isoform subtype DQA1 DQB1
DQ α1.2β6.3 DQ6.3v *0102 *0603
DQ α1.3β6.2 DQ6.2v *0103 *0602
DQ α1.2β6.9 DQ6.9 *0102 *0609

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

Serology

DQ6, DQ1, and DQ5 recognition of some Some DQB1* alleles[1]
DQ6 DQ1 DQ5 N
allele % % % size (N)
*0601 64 23 675
*0602 67 30 1 5151
*0603 62 23 2 2807
*0604 59 27 2 1592
*0605 76 13 358
*0609 48 32 3 149

Alleles

HLA DQB1*0601 frequencies
freq
ref. Population (%)
[2] Indig. Australian Cape York 31.3
Indig. Australian Kimberly 30.5
Nauru 28.4
Fiji Viti Levu 26.3
India Bombay 26.3
Papua New Guinea Lowland 26.0
China Guizhou Prov. Miao 25.9
Papua New Guinea Madang 23.1
Kiribati 22.6
Japan 22.0
Indonesia Nusa Tenggara 19.2
India North Hindus 18.7
Japan Hokkaido Wajin 17.0
Uttar Pradesh Hindu 15.1
PNG Lowland Wosera 14.1
Western Samoa & Tokelau 13.7
Pakistan Kalash 13.0
India Lucknow 12.9
China Wuhan 12.8
South Korea (4) 11.4
PNG Highland 10.9
India Delhi 9.0
Iran Baloch 8.0
Mongolia Khalkha 5.5
Lebanon Yuhmur 4.3
Tunisia Ghannouch 4.3
Poland Wielkopolska 4.0
Mexico Mazatecans 3.5
Spain E. Andalusia 2.0
Italy Central 1.9
France South East 1.6
England Caucasoid 1.1
Ireland South 0.2
Italy Sardinia 0.1
Brazil Guarani Kaiowa 0.0
Cameroon Saa 0.0

DQB1*0601

DQB1*0601 is generally linked to DQA1*0103 as 6.1 haplotype. This haplotype is more common in Japan and other parts of East Asia.

HLA DQB1*0602 frequencies
freq
ref. Population (%)
[2] Spain Pas Valley 31.5
Cameroon Saa 30.8
Congo Kinshasa Bantu 30.0
PNG E. Highlands Goroka 29.8
Siberia Ket Lower Yenisey 29.4
Spain North Cabuernigo 28.9
Russia Arkhangelsk Pomors 24.7
Spain North Cantabrian 24.7
Ireland South 19.6
Belgian (2) 19.4
Siberia Kushun Buryat 18.0
Finland 17.1
Siberia Kets Sulamai Village 17.0
Poland Wielkopolska 16.9
German Essen 16.7
Sp. Basque Arratia Valley 16.7
Denmark 16.6
France Ceph 15.7
Kenya 14.6
England Caucasoid 14.4
Sweden 14.1
France Rennes 13.8
Tunisia Matmata Berber 11.7
Jordan Amman 10.7
Japan Hokkaido Wajin 10.0
Saudi A. Guraiat & Hail 8.4
Japan Central 8.2
Nauru 8.2
Georgia Svaneti Svans 8.1
France South East 8.0
Ethiopia Amhara 7.7
Algeria Oran 7.6
Slovenia 7.5
South Korea (1) 7.4
Japan Fukuoka 6.4
Pakistan Kalash 5.8
China Xinjiang Uygur 5.4
Papua New Guinea Lowland 5.2
Mongolia Khalkh Ulaanbaatar 4.9
Spain Murcia 4.8
India Bombay 4.2
Japan 4.0
Greece (2) 3.3
Israel Arabs 2.3
Vietnam Hanoi Kinh 2.0
Israel Jews 1.5
Mongolia Khoton Tarialan 1.2
USA Alaska Yupik Natives 0.8
Mexico Mixtec Oaxaca 0.5
Italy Sardinia pop2 0.1

DQB1*0602

DQB1*0602 is commonly linked to DQA1*0102 to form 6.2 haplotype. DQ6.2 and is common from Central Asia into Western Europe, *0602 is also linked to DQA1*0103 in parts of Asia.

HLA DQB1*0603 frequencies
freq
ref. Population (%)
[2] Georgia Svaneti Svans 14.4
France West 11.0
Netherlands 10.6
German Essen 9.2
Czech Republic 9.0
Spain Murcia 8.7
Slovakia 8.4
Denmark 8.3
India Lucknow 8.3
Jordan Amman 8.3
France Rennes 8.1
Poland Wielkopolska 8.0
Saudi Arabia Guraiat & Hail 8.0
Tunisia Jerba Berber 7.8
Uganda Muganda Baganda 7.4
Spain North Cantabrian 7.2
Finland 7.1
France South 6.9
China Xinjiang Uygur 6.5
Russia Northwest Slavic 6.0
Ireland Donegal 5.3
Greece (3) 5.2
Ireland Northern (2) 4.9
Italy Rome 4.0
CAR Aka Pygmies 3.6
Lebanon Kafar Zubian 3.2
Sweden 2.5
Thailand 2.1
China Wuhan 1.7
Japan (2) 1.0
South Korea (3) 0.9
Malaysia 0.6

DQB1*0603

DQB1*0603 is commonly linked to DQA1*0103 as 6.3 and is common from Central Asia into Western Europe, *0603 is also linked to DQA1*0102 in parts of Asia. In Europe it is most common in the Netherlands.

HLA DQB1*0604 frequencies
freq
ref. Population (%)
[2] Ethiopia Amhara 10.7
Rwanda Kigali Hutu and Tutsi 10.7
Ethiopia Oromo 10.2
Japan 8.0
Saudi Arabia Guraiat & Hail 8.0
Iran Yazd Zoroastrians 6.9
CAR Aka Pygmies 6.5
South Korea (2) 6.5
Sweden 6.1
Netherlands 5.6
Uganda Muganda Baganda 5.3
Lebanon Niha el Shouff 4.9
Denmark 4.6
France Rennes 4.6
Israel Gaza Palestinians 3.9
China Xinjiang Uygur 3.8
Algeria1 3.5
Russia Northwest Slavic 3.5
England Caucasoid 3.1
German Essen 2.6
Czech Republic 2.4
Greece 2.0
India Delhi 1.8
Nauru 1.5
Finland 1.4
Gambia 0.7

DQB1*0604

DQB1*0604 is found at higher frequencies in parts Africa and Asia and is linked almost exclusively to DQA1*0102 as 6.4. This haplotype is found at its highest Eurasian frequencies in Japan.

HLA DQB1*0609 frequencies
freq
ref. Population (%)
[2] Rwanda Kigali Hutu & Tutsi 5.7
Kenya 5.3
Uganda Muganda Baganda 5.3
Congo Kinshasa Bantu 4.4
Gambia 4.4
Mongolia Tsaatan 4.2
South Korea (3) 3.7
Cameroon Saa 3.5
Slovenia 3.0
Tunisia 3.0
Zimbabwe Harare Shona 2.2
Vietnam Hanoi Kinh 2.0
Netherlands 1.7
Saudi Arabia Guraiat & Hail 1.6
Algeria Oran 1.5
Greece (2) 1.2
Thailand (2) 1.2
Tunisia Matmata Berber 1.2
Italy Rome 1.0
Spain Granada 0.7
Italy Bergamo 0.6
Ireland South 0.2
China Ürümqi Uygur 0.0
USA Alaska Yupik Natives 0.0

DQB1*0609

DQB1*0609 is found in Africa and proximal regions of Eurasia.

Haplotypes and disease

Susceptibility to Leptospirosis infection was found associated with undifferentiated DQ6.[3] Whereas DQ6 was protective against death (or need for liver transplantion) in primary sclerosing cholangitis.[4]

DQ6.1

DQA1*0103:DQB1*0601 (DQ6.1) is found at increased frequencies in Asia and is almost absent in Western Europe. It confers protection from narcolepsy,[5] juvenile diabetes,[6][7] Vogt-Koyanagi-Harada (VKH) syndrome,[8] pemphigus vulgaris,[9] multiple sclerosis,[10] myasthenia gravis.

DQ6.2

DQ6.2 (DQA1*0102 : DQB1*0602) is commonly linked to DR15 and as such is part of the HLA B7-DR15-DQ6 haplotype. This haplotype is considered to be the longest multigene haplotype known within the human genome as it covers over 4.7 million nucleotides. The DR15-DQ6.2 haplotype is the most common DR-DQ haplotype in Europe, and approximately 30% of Americans carry at least DQ6.2. The haplotype is even more common in Central Asia.

DQ6.2 associations with disease

For myasthenia gravis, recognition α34-49 of AChR increased with DQ6.2.[11] DQA1*0102 increases risk cervical cancer.[12][13] In multiple sclerosis DQA1*0102 was the most frequent allele and DQB1*0602 increased significantly in the MS patients.[14][15][16]

Protective effects of DQ6.2

In primary biliary cirrhosis DQ6.2 appears to have a negative association with disease.[17] DQ6.2 also appears to have a protective effect in juvenile diabetes.[18][19] DQ6.2 is also protective against infantile spasms in mestizos.[20]

DQ6.3

DQ6.3 (DQA1*0103 : DQB1*0603) is found in northcentral Europe at moderate frequencies, it is a protective against many autoimmune diseases. It also affords some protection to HIV infection.[21]

DQ6.4

DQ6.4 (DQA1*0102 : DQB1*0604) might be associated with thymoma-induced myasthenia gravis.[22]

References

  1. ^ Allele Query Form IMGT/HLA - European Bioinformatics Institute
  2. ^ a b c d e Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database". Tissue Antigens. 61 (5): 403–407. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660.
  3. ^ Lingappa J, Kuffner T, Tappero J, et al. (May 2004). "HLA-DQ6 and ingestion of contaminated water: possible gene-environment interaction in an outbreak of Leptospirosis". Genes Immun. 5 (3): 197–202. doi:10.1038/sj.gene.6364058. PMID 15014429. S2CID 1771348.((cite journal)): CS1 maint: overridden setting (link)
  4. ^ Boberg KM, Spurkland A, Rocca G, et al. (August 2001). "The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis". Scand. J. Gastroenterol. 36 (8): 886–890. doi:10.1080/003655201750313441. PMID 11495087.((cite journal)): CS1 maint: overridden setting (link)
  5. ^ Hong SC, Lin L, Lo B, et al. (2007). "DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans". Hum. Immunol. 68 (1): 59–68. doi:10.1016/j.humimm.2006.10.006. PMID 17207713.((cite journal)): CS1 maint: overridden setting (link)
  6. ^ Sang Y, Yan C, Zhu C, Ni G (2001). "Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes". Chin. Med. J. 114 (4): 407–9. PMID 11780465.
  7. ^ Saruhan-Direskeneli G, Uyar FA, Bas F, et al. (2000). "HLA-DR and -DQ associations with insulin-dependent diabetes mellitus in a population of Turkey". Hum. Immunol. 61 (3): 296–302. doi:10.1016/S0198-8859(99)00182-2. PMID 10689119.((cite journal)): CS1 maint: overridden setting (link)
  8. ^ Kim MH, Seong MC, Kwak NH, et al. (2000). "Association of HLA with Vogt-Koyanagi-Harada syndrome in Koreans". Am. J. Ophthalmol. 129 (2): 173–177. doi:10.1016/S0002-9394(99)00434-1. PMID 10682969.((cite journal)): CS1 maint: overridden setting (link)
  9. ^ Niizeki H, Inoko H, Mizuki N, et al. (1994). "HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method". Tissue Antigens. 44 (4): 248–251. doi:10.1111/j.1399-0039.1994.tb02390.x. PMID 7871526.((cite journal)): CS1 maint: overridden setting (link)
  10. ^ Amirzargar A, Mytilineos J, Yousefipour A, et al. (1998). "HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients". Eur. J. Immunogenet. 25 (4): 297–301. doi:10.1046/j.1365-2370.1998.00101.x. PMID 9777330.((cite journal)): CS1 maint: overridden setting (link)
  11. ^ Deitiker PR, Oshima M, Smith RG, Mosier DR, Atassi MZ (2006). "Subtle differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides may suffice to mediate myasthenia gravis". Autoimmunity. 39 (4): 277–288. doi:10.1080/08916930600738581. PMID 16891216. S2CID 23462117.
  12. ^ Ghaderi M, Nikitina L, Peacock CS, et al. (October 2000). "Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden". Cancer Epidemiol. Biomarkers Prev. 9 (10): 1067–70. PMID 11045789.((cite journal)): CS1 maint: overridden setting (link)
  13. ^ Schiff MA, Apple RJ, Lin P, Nelson JL, Wheeler CM, Becker TM (2005). "HLA alleles and risk of cervical intraepithelial neoplasia among southwestern American Indian women". Hum. Immunol. 66 (10): 1050–1056. doi:10.1016/j.humimm.2005.09.002. PMID 16386646.
  14. ^ Kolstad A, Hannestad K, Vandvik B, Vartdal F (May 1989). "Multiple sclerosis patients have a high frequency of an HLA-DQ beta epitope defined by a human-human hybridoma antibody". Tissue Antigens. 33 (5): 546–549. doi:10.1111/j.1399-0039.1989.tb01706.x. PMID 2477915.
  15. ^ Amirzargar AA, Tabasi A, Khosravi F, et al. (2005). "Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study". Eur. J. Neurol. 12 (1): 25–30. doi:10.1111/j.1468-1331.2004.00901.x. PMID 15613143. S2CID 11114806.((cite journal)): CS1 maint: overridden setting (link)
  16. ^ Fernández O, Fernández V, Alonso A, et al. (2004). "DQB1*0602 allele shows a strong association with multiple sclerosis in patients in Malaga, Spain". J. Neurol. 251 (4): 440–444. doi:10.1007/s00415-004-0350-2. PMID 15083289. S2CID 6388921.((cite journal)): CS1 maint: overridden setting (link)
  17. ^ Mullarkey ME, Stevens AM, McDonnell WM, et al. (2005). "Human leukocyte antigen class II alleles in Caucasian women with primary biliary cirrhosis". Tissue Antigens. 65 (2): 199–205. doi:10.1111/j.1399-0039.2005.00351.x. PMID 15713222.((cite journal)): CS1 maint: overridden setting (link)
  18. ^ Rayner ML, Kelly MA, Mijovic CH, Barnett AH (March 2002). "Sequencing of the second exon of the MHC class II DQ6 alleles in patients with type 1 diabetes". Autoimmunity. 35 (2): 155–157. doi:10.1080/08916930290016637. PMID 12071438. S2CID 46348916.
  19. ^ Pociot F, McDermott MF (August 2002). "Genetics of type 1 diabetes mellitus". Genes Immun. 3 (5): 235–249. doi:10.1038/sj.gene.6363875. PMID 12140742. S2CID 19983853.
  20. ^ Suastegui RA, De La Rosa G, Carranza JM, Gonzalez-Astiazaran A, Gorodezky C (February 2001). "Contribution of the MHC class II antigens to the etiology of infantile spasm in Mexican Mestizos". Epilepsia. 42 (2): 210–215. doi:10.1046/j.1528-1157.2001.22700.x. PMID 11240591.
  21. ^ Achord AP, Lewis RE, Brackin MN, Henderson H, Cruse JM (1996). "HIV-1 disease association with HLA-DQ antigens in African Americans and Caucasians". Pathobiology. 64 (4): 204–208. doi:10.1159/000164049. PMID 9031330.
  22. ^ Vieira M, Caillat-Zucman S, Gajdos P, Cohen-Kaminsky S, Casteur A, Bach J (1993). "Identification by genomic typing of non-DR3 HLA class II genes associated with myasthenia gravis". J Neuroimmunol. 47 (2): 115–122. doi:10.1016/0165-5728(93)90021-P. PMID 8370765. S2CID 3771373.
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