The genetics of type 2 diabetes
Lindgren CM., Hirschhorn JN.
Type 2 diabetes is the most common form of diabetes, affecting approximately 5-10% of the adult population in the United States [1, 2]. Diabetes is caused by the interaction of multiple environmental and genetic factors and is, therefore, referred to as a complex genetic, polygenic disorder. Despite a great deal of effort, understanding the underlying genetic causes of diabetes has proven difficult. Two main approaches have been taken to try to identify the genes influencing disease: linkage analysis followed by positional cloning and candidate gene association studies. We review the results of these studies and discuss chromosomal regions and genes implicated by using these approaches. We focus on two recent examples, the positional cloning of CAPN10, encoding the calpain 10 protease (originally identified by using linkage analysis and called NIDDM1) [3, 4] , and the association between type 2 diabetes and the Pro12Ala variant in PPARG, encoding peroxisome proliferator activator receptor gamma (PPARγ) [5-7]. These two cases illustrate not only the challenges in determining the genetic causes of type 2 diabetes but also the great promise that modern approaches hold for understanding complex genetic diseases.