Prediction of the risk of type 1 diabetes from polymorphisms in candidate genes.

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease, in which pancreatic beta cells are selectively destroyed. Innate immune response is also important in the development of T1D. Several studies have demonstrated that HLA class II alleles, DQ and DR influence T1D susceptibility. Specific class I and II alleles are non-randomly associated with each other on an extended haplotypes, the typing of which provide the best risk determinants of T1D. Studying the haplotype in different ethnic populations will enable us to identify the exact polymorphisms that can trigger T1D and to develop biological tools for protection. With the advent of numerous candidate markers, additional loci that influence susceptibility to T1D have been reported. Although different studies have suggested that various genetic variants increase the risk, large-scale association studies that examine many polymorphisms simultaneously are required to allow reliable prediction of the genetic risk. Not only the numbers of genetic markers we are applying, but also the accurate phenotyping is critical in the success of setting-up a best-fitting model for prediction. For a better phenotyping, multiple autoantibodies to islet cell antigens, which may arise even before the clinical onset have been known as the best surrogate markers of T1D. However, differences in genotypes between antibody-positive individuals and T1D patients may indicate genetic factors, which determine progression to clinical disease. The ability to detect those antibody-positive individuals who will progress to T1D is central to prevention program.