HLA-DQ6
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.
HLA-DQ6 (MHC Class II, DQ cell surface antigen) | |||
 | |||
| Illustration of HLA-DQ with bound peptide | |||
| 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 | |||
| DQ α1.2β6.3 | DQ6.3v | *0102 | *0603 |
| DQ α1.3β6.2 | DQ6.2v | *0103 | *0602 |
| DQ α1.2β6.9 | DQ6.9 | *0102 | *0609 |
Serology
| 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
| 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.
| 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.
| 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.
| 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.
| 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
- Allele Query Form IMGT/HLA - European Bioinformatics Institute
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.