HLA-DQ7

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DRB1*0301^[1] and the less common HLA DRB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

DQ7 is linked by haplotype to a number of DQA1 (DQ alpha chain) genes, producing in cis-haplotype form, a large number of DQ αβ isoforms. These DQ alpha chains are also known to form transhaplotype isomers with other HLA-DQ.

DQ7 is linked to the following alpha chains genes (DQA1*)

• 03 - *0301, *0302, *0303
• 0401
• 0505
• 0601

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Serology

Serotyping efficiency.

Alleles

DQB1*0301 appears to be associated with lupus anticoagulant.^[3]

Haplotypes

DQ haplotypes of this serotype are formed between the cis-chromosomal genes of the DQA1 locus. This includes DQA1*0301, *0302, *0303, *0401, *0505, *0601.

There is a rather large degree of disequilibration about DQA1*0301 suggesting that this is one of the older and more established HLA DQB1* alleles in Eurasia. The intron structure of DQB1 suggest that DQB1*0301 DQB1*0302/*0303 split occurred before DQB1*0302/*0303, the distribution of *03 in Africa suggest that recombination DQA1*03:DQB1*0301 are primarily the result of recombination events that have occurred in Africa. A recent study of myasthenia gravis in Houston confirms the presence of A*0505:B*0301 in Nigeria. B1*0301 and A1*03 haplotypes are found at relatively high frequencies in SE Asia and Austronesia, also indicating that it is well established in the exo-African population.

DQ7.3

The DQ7.3 haplotype can be formed by DQA1*0301:DQB1*0301, DQA1*0302:DQB1*0301, DQA1*0303:DQB1*0301. In the west, the DQA1*0303:DQB1*0301 haplotype appears to be more common. The gene products of all 3 function similarly and subunits are interchangeable. In the literature, older DNA tests recognize DQA1*0303 as DQA1*0302, and still oldest DNA tests recognize all three as DQA1*03 or DQA1*0301.

DQA1*0303:DQB1*0301 may be involved in narcolepsy.^[5] DQ7.3 appears to be associated with oral ulcerations and gingival disease ^[6]

DQ7.4

DQA1*0401:DQB1*0301 (DQ7.4) This haplotype is found in Siberia, Africa but also at low levels in Western Europe.

DQ7.5

DQA1*0505:DQB1*0301 (DQ7.5) was gene-typed as DQA1*0501:DQB1*0301 until it was recognized that there was amino acid sequence variant in the preprocessed DQA1* gene product (proto-α-chain polypeptide encoded DQA1*0505). This proto-alpha, once processed, is identical to the DQA1*0501 encoded α-chain once it is processed. Almost 100% of DQ7.5 haplotypes carry the DQA1*0505 allele.^[8] The DR5-DQ7.5 is common in the Southeastern Europe and the Levant, with DQ7.5 reaching a haplotype frequency of 40% in Lebanon. Its high level is probably not by chance, the haplotype appears to protect against juvenile diabetes, which appears to be more common among cereal eating peoples.^[9] Cereals were first domesticated in the Near and Middle East more than 10,000 years ago and selection may explain DQ7.5's higher frequencies. (See: Triticeae)

The processed alpha subunit of DQA1*0505 is identical to that of DQA1*0501, but some slight differences in the association with autoimmune disease are observed, possibly as a result of linked DR and DQB1 genes. DQA1*0505 can play into celiac disease under two circumstances. First it can increase risk when DQ2.5 is present, although current studies indicate that it marginally increases risk relative to DQB1*0202 in DQ2.5 cis haplotype. DQA1*0505, without DQ2, is found in a small percentage of coeliac disease (without DQ2 or DQ8).^[10]

DQ7.5 is found also high in frequency in the new world, but with DR types less commonly encountered in the old world. DQA1*05 allele is not clear in the new world. DQB1*0301 may be under current positive selection in the human population, at least in areas where DQ2.5 and DQ8 are high, as it confers resistance to type 1 diabetes. For hepatitis type B, DQ7 is associated with persistence but for C, DQ7 is associated with clearance.^[11] DQA1*0505, DQB1*0301 appear to increase the risk for melanoma in the Spanish population however this may have a linkage to more recent fair skinned migrants. DQB1*0301 is also associated with allergic fungal sinusitis, human papillomavirus (HPV) induced warts, limited cutaneous systemic sclerosis in Africans, and primary sclerosing cholangitis in Southern Europeans. DQB1*0301 is also predisposing in narcolepsy.^[5] DQB1*0301 does not to play a role in any frequently occurring autoimmune disease and its presence in the near east and suppressed frequencies of coeliac disease and Type 1 diabetes in these regions is suggestive that it has a positive selection in Post-Mesolithic cereal based societies in the Western Eurasia.

DQB1*0301 appears to be more associated with early onset myasthenia gravis in Japanese than DQ8, and was also found along with DQB1*0304 to be associated with Chinese MG. DQ7 or associated DR types may play a role in rheumatoid arthritis. In celiac disease the DQ7 (A*0505/1) can mediate celiac disease when HLA DQ2.2 is also present. HLA DQB1*0301 in Turks is associated with Thymoma but the risk may be associated with HLA class I loci.

DQ7.6

DQA1*0601:DQB1*0301 (DQ7.6) is a globally rare haplotype, however it is found at high frequencies in the South Pacific and along the West Pacific rim. DQA1*0301 appears to be uniquely linked to DQA1*0601. DQ7.6 is positively associated with asthma,^[12] pauciarticular juvenile arthritis without anti-nuclear antibodies,^[13] DQ7.6 is negatively associated (Protective against) juvenile diabetes,^[14] liver and spleen disease in Schistosoma japonicum infection,^[15] pulmonary tuberculosis.^[16]

References