Autoimmunity and atherosclerosis: functional polymorphism of PTPN22 is associated with phenotypes related to the risk of atherosclerosis. The Cardiovascular Risk in Young Finns Study

Abstract

Summary There is a growing body of evidence attesting the significance of inflammation in the pathogenesis of atherosclerosis. Protein tyrosine phosphate PTPN22 C/T single nucleotide polymorphism (SNP) at +1858 has been identified recently as a susceptibility factor for various inflammatory autoimmune diseases. We hypothesized that data on the genetic polymorphism of the PTPN22 enzyme associated with an increased risk of autoimmunity could also provide insight into the possible role of autoimmunity in the pathogenesis of atherosclerosis. Therefore we analysed the PTPN22 + 1858 C/T polymorphism in a population of young Finnish adults (n = 2268) for whom data on carotid artery intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, and risk factors for atherosclerosis were available. In males carriage of the T allele of PTPN22 + 1858 was associated significantly with IMT in univariate and multivariate analyses, while in females it was associated with several risk factors for atherosclerosis (BMI, waist circumference, waist-to-hip ratio, serum concentrations of C-reactive protein and triglycerides) but not with IMT. Our results indicate that the genetic polymorphism of PTPN22 + 1858 known to predispose to autoimmunity also enhances the development of atherosclerosis and thereby links the genetics of autoimmunity and atherosclerosis.