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 histocompatibility complex. We investigated the frequency of the BAT2 microsatellite alleles (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) patients, 51 adult-onset IDDM patients, and 85 normal control subjects, and assessed the associations among these BAT2 alleles, TNFa microsatellite alleles (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was significantly 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 control subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the BAT2.9 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 not independent of TNFa polymorphisms.