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. DQ7.3 appears to be associated with oral ulcerations and gingival disease
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. 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.
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). 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. 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.
pauciarticular juvenile arthritis without
anti-nuclear antibodies, DQ7.6 is
negatively associated (Protective against) juvenile diabetes, liver and spleen disease in
Schistosoma japonicum infection,
pulmonary tuberculosis. ==References==