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Gene Review

HLA-DQA2  -  major histocompatibility complex, class II...

Homo sapiens

Synonyms: DX alpha chain, DX-ALPHA, HLA class II histocompatibility antigen, DQ alpha 2 chain, HLA class II histocompatibility antigen, DQ(6) alpha chain, HLA-DQA1, ...
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Disease relevance of HLA-DQA2

  • A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus [1].
  • Trans-encoded DQ alpha beta heterodimers confer susceptibility to myasthenia gravis disease [2].
  • A statistically significant association was observed between alleles of the HLA-DQA2 and of the DR/DQ complex in a DNA-restriction fragment length polymorphism study of 219 members from 21 multiplex families of patients with hyperthyroid Graves' disease and 773 unrelated individuals selected for homozygosity of the HLA-DQA2 alleles [3].
  • Role of predisposing and protective HLA-DQA and HLA-DQB alleles in Sardinian multiple sclerosis [4].
  • Although predisposition to celiac disease is likely to be mediated by a specific DQ alpha/DQ beta heterodimer, a direct role for the DPw1 antigen cannot be discounted [5].

Psychiatry related information on HLA-DQA2

  • Although the effects of minor differences cannot be ruled out completely, it is concluded that there are probably no narcolepsy-specific DR beta or DQ alpha/beta sequences, and that the alleles found in narcolepsy are representative of those found in the healthy population [6].
  • Restriction fragment length polymorphism analysis was performed with several restriction enzymes and three cDNA probes for DQ alpha, DQ beta, and DR beta genes on genomic DNAs obtained from narcoleptics and patients with other sleep disorders, matched controls, and 3 homozygous typing cells representing the DR2 subtypes Dw2, Dw12, and DwAZH [7].
  • The direct connection between the dilated cardiomyopathy and the HLA DQA1 gene confirms the hypothesis on the genetic determinism of this disease [8].

High impact information on HLA-DQA2

  • T cell activation was found to be dependent on both DQ alpha and DQ beta chains [9].
  • These transfectants were constructed using site-directed mutagenesis to introduce nucleotide substitutions into DQ3.2 beta cDNA, followed by retrovirus-mediated gene expression of the mutagenized genes in human B cell lines with different endogenous DQ alpha chains [9].
  • Typing of DNA from 94 unrelated children with celiac disease (CD) with HLA-DQA1 and -DQB1 allele-specific oligonucleotide probes revealed that all but one (i.e., 98.9%) may share a particular combination of a DQA1 and a DQB1 gene [10].
  • To facilitate analysis, we used a parent cell line with a preexisting deletion of one haplotype encompassing DR and DQ alpha and beta [11].
  • This report, based on extensive oligonucleotide dot blot hybridization of PCR-amplified DQA1 and DQB1 genes, reinforces the importance of the Asp57-negative DQ beta chain, but also introduces the possibility that a DQ alpha chain bearing an arginine in position 52 (Arg52) confers susceptibility to IDDM [1].

Chemical compound and disease context of HLA-DQA2


Biological context of HLA-DQA2

  • This indicates that any disease association with HLA-DQA2, at least among DR3;DQ2 individuals, cannot be accounted for solely by polymorphism of the proximal promoter region [13].
  • The DQ subregion contains a pair of closely related A genes, HLA-DQA1 and HLA-DQA2, whose phylogenetic relationship is uncertain, although their generation by duplication of an ancestral A gene before or after speciation can be implied [14].
  • This model strongly suggests that the disease susceptibility correlates quantitatively with the expression at the cell surface of a heterodimer, composed of a DQ alpha-chain bearing an Arg52 and a DQ beta chain lacking an Asp57 [1].
  • The findings support the hypothesis that the presence of a specific DQ alpha/DQ beta heterodimer, encoded in a cis arrangement on HLA-DR3a haplotypes, predisposes to celiac disease [15].
  • There was no apparent predisposing effect of non-aspartic acid residues at position 57 of the DQ beta chain (Asp57-) but there was an excess of homozygous genotypes containing arginine at position 52 of the DQ alpha chain (Arg52+) [16].

Anatomical context of HLA-DQA2


Associations of HLA-DQA2 with chemical compounds

  • Susceptibility to type I diabetes has been shown to be highly correlated with the presence of an amino acid other than Asp at position 57 of the DQ beta-chain (non-Asp57) and also with the presence of an Arg at position 52 of the DQ alpha-chain (Arg52) [21].
  • No significant association was found with the glutamine residue at position 34 of the DQ alpha chain, which was noted previously in MS patients from northern Europe [22].
  • The null allele of the complement component C4 and HLA-DQA2 have been identified as two independent disease susceptibility genes [23].
  • The search for specific structural changes of the DQA and DQB genes has shown that susceptibility correlates with the absence of aspartic acid at position 57 on the DQ beta chain (DQ beta 57 Asp--) and/or the presence of arginine at position 52 on the DQ alpha chain (DQ alpha 52 Arg+) [24].
  • These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQ alpha) and leucine in position 26 (DQ beta) [25].

Regulatory relationships of HLA-DQA2

  • Thus, the celiac disease associated DQA1 and DQB1 genes encode a functionally expressed DQ alpha/beta heterodimer [26].
  • To evaluate the extent of this predicted diversity, DQ2 beta or DQ3.2 beta cDNA were introduced into a panel of homozygous B cell lines that expressed different DQ alpha alleles [27].

Other interactions of HLA-DQA2

  • Previous studies have suggested that the HLA-DQA2 gene may be associated with IDDM [13].
  • In view of the respective positions of the two residues and their charge, we might anticipate that both residues DQ beta Asp57 and DQ alpha Arg52 are critical for modulation of susceptibility, presumably via viral-antigenic peptide and/or autoantigen presentation [1].
  • Taken together, the data suggest that IDDM is primarily associated with several (at least five) different DQ alpha beta heterodimers [28].
  • These two hypotheses were examined using the polymerase chain reaction method to amplify polymorphic sequences from the DQ alpha locus, as well as the DX alpha locus, an homologous but nonexpressed locus, in a series of primates that diverged at known times [29].
  • It has been suggested that the susceptibility to develop MS might be determined by the corresponding DQ alpha-beta heterodimers either encoded in cis or in trans [30].

Analytical, diagnostic and therapeutic context of HLA-DQA2

  • Northern blot analysis of sheep mRNA using exon specific probes for each of the two Ovar-DQA genes show that both genes are transcribed, whereas in humans there is no evidence that HLA-DQA2 is transcriptionally active [31].
  • In an application for HLA-DQA typing a 228 base pair long region of the polymorphic exon 2 of DQA1 gene was amplified and the denatured PCR product distributed into streptavidin-coated microtitration wells together with the detection probe and one of the catching probes [32].
  • We describe here the relationships among detection rates achieved by four DNA typing systems (D1S80 typing, TH01 typing, HLA DQA1 typing, and PM typings), the post-mortem interval, types of specimens (bone, nail, and blood), post-mortem changes, and the site at which the corpse was found (indoors, outdoor, or in the sea) [33].
  • Time-resolved fluorometry based sandwich hybridisation assay for HLA-DQA1 typing [32].
  • The technique consists of PCR amplification of a DNA fragment comprising the second exon of the HLA-DQA1 gene, amplicon denaturation using a low ionic strength solution (LIS), and electrophoresis on a small native polyacrylamide gel, followed by a rapid silver staining procedure [34].


  1. A combination of HLA-DQ beta Asp57-negative and HLA DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus. Khalil, I., d'Auriol, L., Gobet, M., Morin, L., Lepage, V., Deschamps, I., Park, M.S., Degos, L., Galibert, F., Hors, J. J. Clin. Invest. (1990) [Pubmed]
  2. Trans-encoded DQ alpha beta heterodimers confer susceptibility to myasthenia gravis disease. Khalil, I., Berrih-Aknin, S., Lepage, V., Loste, M.N., Gajdos, P., Hors, J., Charron, D., Degos, L. C. R. Acad. Sci. III, Sci. Vie (1993) [Pubmed]
  3. Linkage disequilibrium between the HLA-DQA2 alleles and the HLA/DR/DQ complex. Ratanachaiyavong, S., Bidwell, J.L., Bidwell, E.A., McGregor, A.M. Hum. Immunol. (1991) [Pubmed]
  4. Role of predisposing and protective HLA-DQA and HLA-DQB alleles in Sardinian multiple sclerosis. Marrosu, M.G., Muntoni, F., Murru, M.R., Costa, G., Congia, M., Marrosu, G., Aiello, I., Pirastu, M., Cianchetti, C. Arch. Neurol. (1993) [Pubmed]
  5. Celiac disease is associated with an extended HLA-DR3 haplotype which includes HLA-DPw1. Hall, M.A., Lanchbury, J.S., Bolsover, W.J., Welsh, K.I., Ciclitira, P.J. Hum. Immunol. (1990) [Pubmed]
  6. MHC class II sequences of an HLA-DR2 narcoleptic. Lock, C.B., So, A.K., Welsh, K.I., Parkes, J.D., Trowsdale, J. Immunogenetics (1988) [Pubmed]
  7. Narcolepsy-cataplexy in Israeli Jews is associated exclusively with the HLA DR2 haplotype. A study at the serological and genomic level. Wilner, A., Steinman, L., Lavie, P., Peled, R., Friedmann, A., Brautbar, C. Hum. Immunol. (1988) [Pubmed]
  8. Immunogenetic risk factors of dilated cardiomyopathy. Popovici, M., Groppa, L., Kalinina, L. Blood pressure. Supplement. (1996) [Pubmed]
  9. Polymorphic DQ alpha and DQ beta interactions dictate HLA class II determinants of allo-recognition. Kwok, W.W., Mickelson, E., Masewicz, S., Milner, E.C., Hansen, J., Nepom, G.T. J. Exp. Med. (1990) [Pubmed]
  10. Evidence for a primary association of celiac disease to a particular HLA-DQ alpha/beta heterodimer. Sollid, L.M., Markussen, G., Ek, J., Gjerde, H., Vartdal, F., Thorsby, E. J. Exp. Med. (1989) [Pubmed]
  11. HLA class II regulation and structure. Analysis with HLA-DR3 and HLA-DP point mutants. Pious, D., Dixon, L., Levine, F., Cotner, T., Johnson, R. J. Exp. Med. (1985) [Pubmed]
  12. HLA-DQA and DQB alleles contribute to susceptibility to insulin-dependent diabetes mellitus. Wang, H., He, R. Chin. Med. Sci. J. (1993) [Pubmed]
  13. Limited polymorphism of the HLA-DQA2 promoter and identification of a variant octamer. Rudy, G., Lew, A.M. Hum. Immunol. (1994) [Pubmed]
  14. A SINE insertion provides information on the divergence of the HLA-DQA1 and HLA-DQA2 genes. Del Pozzo, G., Guardiola, J. Immunogenetics (1990) [Pubmed]
  15. A family study confirms that the HLA-DP associations with celiac disease are the result of an extended HLA-DR3 haplotype. Bolsover, W.J., Hall, M.A., Vaughan, R.W., Welsh, K.I., Ciclitira, P.J. Hum. Immunol. (1991) [Pubmed]
  16. Strong association between DQA1/DQB1 genotype and early-onset IDDM in Chinese: the association is with alleles rather than specific residues. Chang, Y.W., Lam, K.S., Hawkins, B.R. Eur. J. Immunogenet. (1998) [Pubmed]
  17. The cryptic HLA-DQA2 ("DX alpha") gene is expressed in human B cell lines. Yu, L.P., Sheehy, M.J. J. Immunol. (1991) [Pubmed]
  18. Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. Rønningen, K.S., Gjertsen, H.A., Iwe, T., Spurkland, A., Hansen, T., Thorsby, E. Diabetes (1991) [Pubmed]
  19. Co-amplification of the cystic fibrosis delta F508 mutation with the HLA DQA1 sequence in single cell PCR: implications for improved assessment of polar bodies and blastomeres in preimplantation diagnosis. Wu, R., Cuppens, H., Buyse, I., Decorte, R., Marynen, P., Gordts, S., Cassiman, J.J. Prenat. Diagn. (1993) [Pubmed]
  20. HLA DQ and DP locus mismatches and their effect on MLC in HLA class I- and DRB1-matched unrelated patient/donor pairs waiting for allogeneic bone-marrow transplantation. Partanen, J., Koskimies, S. Scand. J. Immunol. (1994) [Pubmed]
  21. HLA-DQA1 and DQB1 gene polymorphisms in type I diabetic patients from central Italy and their use for risk prediction. Buzzetti, R., Nisticò, L., Osborn, J.F., Giovannini, C., Chersi, A., Sorrentino, R. Diabetes (1993) [Pubmed]
  22. Analysis of HLA-class II DQA1, DQB1, DRB1 and DPB1 in Italian multiple sclerosis patients. Ciusani, E., Allen, M., Sandberg-Wollheim, M., Eoli, M., Salmaggi, A., Milanese, C., Nespolo, A., Gyllensten, U. Eur. J. Immunogenet. (1995) [Pubmed]
  23. Immunologic aspects of scleroderma. White, B. Current opinion in rheumatology. (1994) [Pubmed]
  24. The role of genetic predisposition to type I (insulin-dependent) diabetes mellitus. Deschamps, I., Beressi, J.P., Khalil, I., Robert, J.J., Hors, J. Ann. Med. (1991) [Pubmed]
  25. Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus. Skarsvåg, S., Hansen, K.E., Moen, T., Eggen, B.M. Scand. J. Immunol. (1995) [Pubmed]
  26. T lymphocyte recognition of a celiac disease-associated cis- or trans-encoded HLA-DQ alpha/beta-heterodimer. Lundin, K.E., Sollid, L.M., Qvigstad, E., Markussen, G., Gjertsen, H.A., Ek, J., Thorsby, E. J. Immunol. (1990) [Pubmed]
  27. A genetically controlled pairing anomaly between HLA-DQ alpha and HLA-DQ beta chains. Kwok, W.W., Thurtle, P., Nepom, G.T. J. Immunol. (1989) [Pubmed]
  28. Distribution of HLA-DRB1, -DQA1 and -DQB1 alleles and DQA1-DQB1 genotypes among Norwegian patients with insulin-dependent diabetes mellitus. Rønningen, K.S., Spurkland, A., Iwe, T., Vartdal, F., Thorsby, E. Tissue Antigens (1991) [Pubmed]
  29. Ancient roots for polymorphism at the HLA-DQ alpha locus in primates. Gyllensten, U.B., Erlich, H.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  30. HLA class II-associated genetic susceptibility in multiple sclerosis: a critical evaluation. Olerup, O., Hillert, J. Tissue Antigens (1991) [Pubmed]
  31. Nucleotide sequence, polymorphism, and evolution of ovine MHC class II DQA genes. Scott, P.C., Gogolin-Ewens, K.J., Adams, T.E., Brandon, M.R. Immunogenetics (1991) [Pubmed]
  32. Time-resolved fluorometry based sandwich hybridisation assay for HLA-DQA1 typing. Sjöroos, M., Ilonen, J., Reijonen, H., Lövgren, T. Dis. Markers (1998) [Pubmed]
  33. Influence of post-mortem changes on DNA typing (D1S80, TH01, HLA DQA 1, and PM typing system): case studies for personal identification. Fujita, Y., Kubo, S., Tokunaga, I., Kitamura, O., Gotohda, T., Ishigami, A. Legal medicine (Tokyo, Japan) (2004) [Pubmed]
  34. HLA-DQA1 allele typing by nonisotopic PCR-LIS-SSCP. Abba, M.C., Gómez, M.A., Golijow, C.D. Braz. J. Med. Biol. Res. (2001) [Pubmed]
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