Purpose of review: A variation in the gene encoding the cysteine protease calpain 10 (CAPN10) was recently linked and associated with type 2 diabetes by positional cloning. This positional cloning was a follow-up investigation to the identification of a diabetes-linked region on human chromosome 2 identified by genome-wide scanning a few years earlier. In this paper we give a general background on the genetic studies performed on CAPN10 to date, and review the most recent studies on the functional role of calpain 10.
Recent finding: A haplotype or haplotype combination comprising three intronic single nucleotide polymorphisms (UCSNP-43, 19, and 63) were associated with a threefold increased risk of type 2 diabetes in the population in which linkage was first found. Another polymorphism, UCSNP-44, which is in linkage disequilibrium with a coding single-nucleotide polymorphism (Thr504Ala), has subsequently been associated with type 2 diabetes in extensive meta-analyses. Meanwhile, initial studies probing the possible role of calpain-10, completely unknown at the time, are now being pursued, both in isolated cells and humans.
Summary: The positional cloning of CAPN10 as a candidate gene for type 2 diabetes has been particularly fruitful. Not only has it identified an important and surprising piece of the puzzle underlying the development of diabetes, but it has also modelled and paved the way for investigations concerning complex genetic diseases other than type 2 diabetes.