Common variants in genes regulating free fatty acid metabolism and risk of type 2 diabetes and cardiovascular disease

Abstract

The present study evaluated genetic and metabolic factors influencing the risk for type 2 diabetes and cardiovascular disease (CVD) with special reference to increased concentrations of free fatty acids (FFA) in 1174 Swedish diabetic and nondiabetic subjects. Common polymorphisms in the fatty acid binding protein 2 (FABP2), the B2-adrenergic receptor (B2-AR), the B3 -adrenergic receptor (B3-AR) and the uncoupling protein 1 (UCP-1) genes were related to anthropometric and metabolic variables. We found that nondiabetic subjects with increased FFA concentrations had an increased prevalence of myocardial infarction and stroke in their parents. Subjects with the Thr54 allele in the FABP2 gene had increased triglyceride and cholesterol concentrations and increased prevalence of stroke in their parents. The Gln27 allele in the B2-AR gene was more frequent in diabetic patients than among nondiabetic subjects. In sibling pairs discordant for the B2-AR polymorphism, siblings with more Gln27 alleles had increased insulin and FFA concentrations. Siblings with the Trp64Arg64 genotype in B3-AR gene had higher 2-h glucose and FFA concentrations compared with siblings with the Trp64Trp64 genotype. Siblings with the A variant (-3826) in the UCP-1 gene had elevated blood pressure and increased glucose and FFA concentrations. In summary, increased FFA concentrations influence the risk for both type 2 diabetes and CVD and common polymorphisms in genes involved in FFA metabolism increase susceptibility to type 2 diabetes.