Identification of New Susceptibility Genes for Type 1 Diabetes: An Update

Abstract

With a relative failing of linkage and candidate gene association studies, there has been much sceptism about the ability of geneticists to identify genes for common, complex disorders. In the field of the genetics of type 1 diabetes (T1D), more than twenty years of labor-intensive and cost-expensive effort has resulted in the identification of only four T1D- predisposing loci, which are as follows: Human Leucocyte Antigens (HLA) class II, insulin gene region, cytotoxic T-lymphocyte associated 4 (CTLA-4), and protein tyrosine phosphatase, non-receptor member 22 (PTPN22). Recent technological advances and a better understanding of the genetic architecture of complex diseases has led to the development of the genome-wide association (GWA) study, which is a powerful new approach to identifying genes influencing predisposition to common, complex disease. For T1D, the implication of the GWA approach in 2005 resulted in rapid progress in the discovery of new etiological variants. To date, the involvement in T1D pathogenesis is proven for several new genes such as interleukin 2 receptor alpha (IL2RA/CD25), interferon-induced helicase domain 1 (IFIH1), and small ubiquitin-related modifier 4 (SUMO4). An extended list of likely candidates for T1D susceptibility identified through the GWA approach includes PTPN2, CD226, PPARG2, IL2/IL21, ADAM33, and some other genes. A great benefit to clinical medicine is expected in the years to come, and whilst prediction of disease and pharmacogenetics may eventually prove valuable, the greatest clinical benefit of GWA studies is likely to come from etiological insights into disease processes. Keywords: Genome-wide association, susceptibility, type 1 diabetes