title: Human leukocyte antigen class I B and C loci contribute to Type 1 Diabetes (T1D) susceptibility and age at T1D onset.
abstract: Alleles of human leukocyte antigen (HLA) class II genes are well known to affect susceptibility to type 1 diabetes (T1D), but less is known about the contribution of HLA class I alleles to T1D susceptibility. In this study, molecular genotyping was performed at the HLA-B and HLA-C loci for 283 multiplex Caucasian families, previously typed for HLA-A and the class II loci. Allele frequencies were compared between affected siblings and affected family-based controls. Linkage disequilibrium coefficients were calculated for HLA-B-HLA-C haplotypes and for class I-lass II haplotypes. After adjustment for linkage disequilibrium, the following alleles remain associated with T1D: B*1801, B*3906, B*4403, C*0303, C*0802, and C*1601. B and C allele associations were tested for certain T1D-associated DRB1-DQB1 haplotypes, with the following results: B*3801 is protective on DRB1*0401-DQB1*0302 haplotypes, both C*0701 and C*0702 are predisposing on DRB1*0404-DQB1*0302 haplotypes, and B*3906 is predisposing on DRB1*0801-DQB1*0402 haplotypes. As with previous results for HLA-A, HLA-B and HLA-C are associated with age at T1D onset (mean 11.6 +/- 0.3 years). The protective allele B*4403 was associated with older age at onset (15.1 years; p < 0.04), and the predisposing alleles C*0702 and B*3906 were associated with younger age at onset (9.5 years, p < 0.001; and 7.8 years, p < 0.002, respectively). These data support a role for HLA class I alleles in susceptibility to and age at onset of T1D.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Janelle A
authors.initials: JA
authors.lastname: Noble
mesh_terms: D017668:Age of Onset; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D016017:Odds Ratio
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II