Association of the PTPN1 gene with type 2 diabetes and insulin resistance.

Extract: An extensive body of evidence suggests that genes are major contributors to type 2 diabetes (T2DM) susceptibility. Until recently efforts to identify T2DM genes have met with limited success. Application of recent advances in high throughput genetics and genetic analysis has revealed evidence for association of protein tyrosine phosphatase N1 gene (PTPN1, a catalytic protein that removes phosphate groups from phosphorylated tyrosine residues) with T2DM and insulin resistance (a condition whereby the body no longer responds to insulin). The evidence suggests that this association is mediated by DNA sequence differences outside the coding region of the PTPN1 gene. Over 10 different genetic studies have concluded that the long arm of human chromosome 20 (20q) is linked to the inheritance of diabetes. One gene that is located in 20q is PTPN1, which encodes the PTP1B protein, a ubiquitously expressed phosphatase (protein tyrosine phosphatase 1B), which dephosphorylates phosphorylated tyrosine residues of the active insulin receptor protein thereby disrupting the insulin signaling pathway.