HLA-DQ6 (DQ6) is a human leukocyte antigenserotype 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]
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.
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.
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.
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]
DQ6.2 (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.
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]
^Lingappa J, Kuffner T, Tappero J, Whitworth W, Mize A, Kaiser R, McNicholl J (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. PMID15014429. S2CID1771348.
^Boberg KM, Spurkland A, Rocca G, Egeland T, Saarinen S, Mitchell S, Broomé U, Chapman R, Olerup O (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. PMID11495087.
^Hong SC, Lin L, Lo B, Jeong J, Shin Y, Kim S, Kweon Y, Zhang J, Einen M (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. PMID17207713.
^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. PMID11780465.
^Saruhan-Direskeneli G, Uyar FA, Bas F, Günöz H, Bundak R, Saka N, Darendeliler F (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. PMID10689119.
^Kim MH, Seong MC, Kwak NH, Yoo JS, Huh W, Kim TG, Han H (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. PMID10682969.
^Niizeki H, Inoko H, Mizuki N, Inamoto N, Watababe K, Hashimoto T, Nishikawa T (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. PMID7871526.
^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. PMID16386646.
^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. PMID2477915.
^Amirzargar AA, Tabasi A, Khosravi F, Kheradvar A, Rezaei N, Naroueynejad M, Ansaripour B, Moradi B, Nikbin B (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. PMID15613143. S2CID11114806.
^Fernández O, Fernández V, Alonso A, Caballero A, Luque G, Bravo M, León A, Mayorga C, Leyva L (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. PMID15083289. S2CID6388921.
^Mullarkey ME, Stevens AM, McDonnell WM, Loubiere L, Brackensick J, Pang J, Porter A, Galloway D, Nelson J (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. PMID15713222.
^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. PMID12071438. S2CID46348916.
^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. PMID9031330.
^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. PMID8370765. S2CID3771373.
