Age-related association of MHC class I chain-related gene A (MICA) with type 1 (insulin-dependent) diabetes mellitus

To assess the contribution of the HLA class I region to susceptibility to a nd heterogeneity of type 1 diabetes, we investigated the association of pol ymorphism of MHC class I chain-related gene A (MICA) with age-at-onset as w ell as susceptibility to type 1 diabetes. One hundred one Japanese patients and 110 healthy control subjects were studied. The frequency of A4 allele was significantly higher and that of AG allele was significantly lower in p atients than in control subjects. The frequency of A5.1 allele was highest in early-onset patients (23.0%), intermediate in intermediate-onset patient s (9.2%) and lowest in late-onset patients (7.7%) (trend chi-squared test, p = 0.0098). A5.1 allele was strongly associated with HLA-B7 and Cw7, sugge sting that MICA*A5.1-B7-Cw7 haplotype contains a gene responsible for age-a t-onset. A4 allele was associated with a susceptible haplotype, DR4-DQB1*04 01, and AG allele was associated with a protective haplotype, DR2-DQB1*0601 , suggesting that the association of MICA with type 1 diabetes susceptibili ty may be due to linkage disequilibrium with class II haplotypes. These dat a suggest that MICA gene is associated with age-at-onset and that a gene (o r genes) responsible fur age-at-onset of type 1 diabetes is located in the HLA class I region, probably near the region of MICA-B-C. (C) American Soci ety for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.