Genetics of type 2 diabetes in Asian Indians

Abstract

Type 2 diabetes (T2D) is a polygenic disorder with multiple genes located on different chromosomes contributing to its susceptibility. Analysis of the genetic factors is further complicated by the fact that numerous environmental factors interact with genes to produce the disorder. Only a minority of cases of T2D such as maturity-onset diabetes of the young are caused by single gene defects. As Asian Indians have an increased susceptibility to diabetes and have increased insulin resistance, they are a unique population for carrying out genetic studies. Asian Indians develop T2D at lower levels of BMI, one to two decades earlier and have stronger heritability factors compared with Europeans. All these factors point to the role of possible ethnic variations in genetic susceptibility. Recent genetic studies on Asian Indians indicate that certain genes appear to predispose Indians to diabetes while other genes, which afford protection against diabetes and insulin resistance to Caucasians, do not appear to protect Indians. In addition, there are several genes (e.g., TCF7L2), which are similar in Asian Indians and in Europeans, that contribute to susceptibility to T2D. Advances in genotyping techniques and the availability of large patient cohorts have made it possible to identify common genetic variants associated with T2D through genome-wide association studies. Recent studies have shown that common genetic variations contribute to T2D risk within populations but do not explain the difference between populations. In this context, the risk allele evaluation of T2D in Asian Indians could help provide better understanding of increased susceptibility to T2D within this ethnic group.