Genes of the immune system cosegregate with the age at onset of diabetes in the BB/OK rat

The knowledge of genetic factors determining the age at onset of diabetes may help to delay the development of diabetes and its complications. This prompted us to use our well-characterized BE/OK rat whose age at onset of diabetes can change from 50 to more than 400 days for crossing studies to search for loci cosegregating with the age at onset, Fifty-nine diabetic first backcross hybrids resulting from crosses between diabetic BE/OK and diabetes-resistant DA and SHR rats were genotyped with PCR-analyzed microsatellite markers located on 21 chromosomes. Loci on chromosomes 6 (Ighe -D6Mgh2) and 8 (D8Mit2- Apoc3) were linked with the age at onset, Hybrids which were homozygous for the BE alleles developed significantly earlier diabetes than hybrids which were heterozygous, The difference between the age at onset of heterozygous and homozygous hybrids reached a maximum at the loci Ighe on chromosome 6 (+32 days, p=0.0018) and D8Mit2 on chromosome 8 (+28 days, p=0.007). Candidate genes around the loci linked with the age at onset of diabetes are involved in the humoral and cellular immune response. For the first time, this study provides evidence that genetic factors can affect the age at onset of diabetes in the rat. (C) 1998 Academic Press.