title: Susceptibility to type 1 (insulin-dependent) diabetes mellitus in Spanish patients correlates quantitatively with expression of HLA-DQ alpha Arg 52 and HLA-DQ beta non-Asp 57 alleles.
abstract: HLA-DQ alpha and beta alleles were chosen as the most sensitive Type 1 (insulin-dependent) diabetes mellitus susceptibility markers for evaluating the disease associations and Type 1 diabetes risk in a population-based registry from Madrid. The absence of aspartic acid in position 57 of the DQ beta chain (non-Asp 57), and the presence of arginine in position 52 of the DQ alpha chain (Arg 52) were found to be reliable markers of Type 1 diabetes susceptibility among the Spanish population, with significantly higher frequencies among the cases of Type 1 diabetes compared to randomly selected non-diabetic control subjects from the general Madrid population. While non-Asp 57 homozygosity conferred an absolute risk of 32.3 per 100,000 per year and Arg 52 of 31.5 per 100,000 per year, the risk for double homozygotes for both non-Asp 57 and Arg 52 was estimated as 101.7 per 100,000 per year. Individuals homozygous for only one of these alleles, and heterozygous at the other locus, had a markedly lower Type 1 diabetes risk (12.8 per 100,000 per year), approximating the general population incidence for Madrid. Thus, susceptibility to Type 1 diabetes in Spanish patients is associated, quantitatively, with non-Asp 57 DQ beta and Arg 52 DQ alpha alleles.
authors.affiliation: Hospital Clinico San Carlos, Universidad Complutense, Madrid, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Gutierrez-Lopez
authors.forename: S
authors.initials: S
authors.lastname: Bertera
authors.forename: M T
authors.initials: MT
authors.lastname: Chantres
authors.forename: C
authors.initials: C
authors.lastname: Vavassori
authors.forename: J S
authors.initials: JS
authors.lastname: Dorman
authors.forename: M
authors.initials: M
authors.lastname: Trucco
authors.forename: M
authors.initials: M
authors.lastname: Serrano-Rios
mesh_terms: D000483:Alleles; D001120:Arginine; D001224:Aspartic Acid; D001483:Base Sequence; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006720:Homozygote; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D001224:Aspartic Acid; D001120:Arginine