Abstract
The HLA-DQA1 and DQB1 genes have recently been recognized to be strong genetic markers of susceptibility to type 1 (insulin-dependent) diatetes mellitus. The Arg52 DQA1 and non-Asp57 DQB1 alleles of these genes correlate with the disease predisposition and the Asp57 DQB1 and non-Arg52 DQA1 alleles with disease protection. We investigated 113 patients with type 1 diabetes and 121 healthy subjects from the Russian population of Moscow using DNA amplification and dot-blot hybridization with sequence-specific oligonucleotides (SSO). Using conventional statistical methods we confirmed previous observations indicating the important role of the abovementioned amino acid residues in susceptibility and resistance to type 1 diabetes. Relative risk values for all alleles and absolute risk for carriers of most predisposing allele combinations were calculated. The absolute risk for carriers of DQA1 and DQB1 gene alleles allowing for the formation of four possible ‘diabetogenic’ heterodimers on the surface of immunocompetent cells, regardless of the type of coding (cis ortrans), was 2.54%, which is 13 times greater than the background risk for the Russian population −0.2% up to 30 years of age.
Similar content being viewed by others
References
Eisenbarch GS, Type 1 diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368, 1986
Rossini A, Mordes J, Live A, Immunology of IDDM. Annu Rev Immunol 3:289–320, 1985
Berger W, Calabri F, Garotta G, Neri T, Ceppellini R, HLA and insulin-dependent diabetes mellitus: high risk for Drw3/Drw4 heterozygous and segregation in B/DR recombinant family. In: Histocompatibility testing 1980. Springer, Berlin Heidelberg New York, p 948, 1980
Sterkers J, Zeliszewski D, Chaussee A, HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes. Proc Natl Acad Sci USA 85:6473–6477, 1988
Todd J, Bell J, McDevitt H, DQ beta gene contributes to susceptibility and resistance to IDDM. Nature 329:599–604, 1987
Morel P, Dorman J, Todd J, McDevitt H, Trucco M, Aspartic acid at position 57 of the HLA-DQβ chain protects against type 1 diabetes: A family study. Proc Natl Acad Sci USA 85:8111–8115, 1988
Ronningen K, Iwe T, Halstensan T, Spurkland A, Thorsby E, The amino acid at position 57 at the HLA-DQβ chain and susceptibility to develop insulin-dependent diabetes mellitus. Hum Genet 26:215–225, 1989
Reijonen H, Ilonen J, Knip M, Akerblom H, HLA-DQB1 alleles and absence of Asp57 as susceptibility factors of IDDM in Finland. Diabetes 40:1640–1644, 1991
Jenkins D, Mijovic C, Fletcher J, Jacobs K, Bradwell A, Barnett A, Identification of susceptibility loci for type 1 (insulin-dependent) diabetes mellitus by trans-racial gene mapping. Diabetologia 33:387–395, 1990
Awata T, Kuzuya T, Matsuda A, Iwamoto Y, Kanezawa H, Genetic analysis of HLA class II alleles and susceptibility to type 1 (insulin-dependent) diabetes mellitus in Japanese subjects. Diabetologia, 35:419–424, 1992
Khalil I, d'Auriol L, Gobet M, Morin L, Lepage V, Deschamps I, Park M, Degos L, Galibert F, Hors J, A combination of HLA-DQ beta Asp57-negative and HLA-DQ alpha Arg52 confers susceptibility to insulin-dependent diabetes mellitus. J Clin Invest 85:1315–1319, 1990
Khalil I, Deshamps I, Lapage V, Al-Daccak R, Degos L, Hors J, Dose effect of cis- and trans-encoded HLA-DQα/β heterodimers in IDDM susceptibility. Diabetes 41:378–384, 1992
Gutierrez-Lopez M, Bertera S, Chantres M, Vavassori C, Dorman J, Trucco M, Serrano-Rios M, Susceptibility to type 1 (insulin-dependent) diabetes mellitus in Spanish patients correlates quantitatively with expression of HLA-DQα Arg52 DQβ non-Asp57 alleles. Diabetologia 35:583–588, 1992
Charron D, Lotteau V, Turmel P, Hybrid HLA-DC antigens provide molecular evidence for gene transcomplementation. Nature 312:157–159, 1984
Nepom B, Schwartz D, Palmer J, Nepom G, Transcomplementation of HLA genes in IDDM: HLA-DQ α- and β-chains produce hybrid molecules in DR3/4 heterozygotes. Diabetes 36:114–117, 1987
Maniatis T, Fritsch E, Sambrook J, Molecular clonning. A Laboratory manual. Cold Spring Harbor Laboratory, New York, 1982
Saiki R, Scharf S, Faloona F, Mullis K, Horn G, Erlich H, Arnheim N, Enzymatic amplification of β-globin genomic gene sequence and restriction site analysis for diagnosis of sickle cell anaemia. Science 230:1350–1354, 1985
Bugawan T, Erlich H, Rapid typing of HLA-DQB1 DNA polymorphism using nonradioactive oligonucleotide probes and amplified DNA. Immunogenetics 33:163–170, 1991
Ovchinnikov I, Gavrilov D, Nosikov V, Debabov V, The use of polymerase chain reaction for HLA-DQA1 typing with allelespecific oligonucleotide probes (in Russian). Molekulyarnaya biologia 25:1266–1272, 1991
Meinkoth J, Wahl G, Hybridization of nucleic acids immobilized on solid supports. Anal Biochem 138:267–284, 1984
Li C, First course in population genetics. The Boxwood Press, Pacific Grove, 1976
Haldane J, The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet 20:309–313, 1956
Babadjanova G, Sergeyev A, Kuraeva T, Mazovetsky A, Genetic analysis of the structure of liability to diabetes mellitus (in Russian). Genetika 26:2051–2057, 1990
Trucco M, Dorman J, Immunogenetics of insulin-dependent diabetes mellitus. Crit Rev Immunol 9:201–245, 1989
Dorman J, LaPorte R, Stone R, Trucco M, Worldwide differences in the incidence of type 1 diabetes are associated with amino acid variation at position 57 of the HLA-DQβ chain. Proc Natl Acad Sci USA 87:7370–7374, 1990
Lo S, Tun R, Leslie R, Non-genetic factors causing type 1 diabetes. Diabet Med 8:609–618, 1991
Bingley P, Bonifacio E, Gale E, Can we really predict IDDM? Diabetes 42:213–220, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gavrilov, D.K., Kuraeva, T.L., Dedov, I.I. et al. Frequency analysis of HLA-DQA1 and HLA-DQB1 gene alleles and susceptibility to type 1 diabetes mellitus in Russian patients. Acta Diabetol 31, 82–86 (1994). https://doi.org/10.1007/BF00570540
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00570540