Gene variants, insulin resistance, and dyslipidaemia

PURPOSE OF REVIEW: Both insulin resistance and dyslipidaemia are determined by genetic and environmental factors. Depending on their expression and their function, gene variants (mutations, polymorphisms) can primarily regulate either insulin action or dyslipidaemia. The purpose of this review is to give some examples from recent studies on gene variants regulating primarily insulin signalling or lipoprotein metabolism. RECENT FINDINGS: Common polymorphisms in the PC-1, insulin receptor substrate 1 and 2, and PPAR-gamma 2 genes have been linked to insulin resistance and dyslipidaemia, although the results have not been consistent. However, the Pro12Pro genotype of the PPAR-gamma 2 gene has been consistently associated with insulin resistance and the risk of type 2 diabetes. Promoter polymorphisms in the hepatic lipase gene, the 54Thr allele of the fatty acid binding protein 2 gene, and genes regulating LDL particle size have been associated with lipid metabolism, but on the other hand their association with insulin resistance is not consistent. SUMMARY: Although results have not always been consistent, gene variants affecting primary insulin action or dyslipidaemia, and particularly their interaction with the environment, are important modulators of glucose and lipoprotein metabolism.