Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus

The BAT2 gene lies within the class III region of the major histocompatibil ity complex. We investigated the frequency of the BAT2 microsatellite allel es (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) pati ents, 51 adult-onset IDDM patients, and 85 normal control subjects, and ass essed the associations among these BAT2 alleles, TNFa microsatellite allele s (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was sign ificantly increased in the young-onset IDDM patients (12.8 vs 4.1%, Pc = 0. 04896), whereas the frequency of BAT2.12 allele was significantly decreased in young-onset IDDM patients (0.0 vs 11.8%, Pc = 0.00002) compared with co ntrol subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the B AT2.9 and HLA-DRB1 alleles. The BAT2.12 allele was strongly associated with TNFa13, and with DRB1*1502 in control subjects. These results suggest that the BAT;! microsatellite polymorphism is associated with the age-at-onset of IDDM and possibly with the inflammatory process of pancreatic beta-cell destruction during: the development of IDDM. However, this association is n ot independent of TNFa polymorphisms.