Polymorphisms in susceptibility genes for type 2 diabetes and obesity predispose to the metabolic syndrome
Document Actions
It is not well established whether different components of the metabolic syndrome phenotype are related through common genetic factors. The study aimed to investigate whether common variations (single nucleotide polymorphisms or SNPs) in 17 genes previously associated with diabetes or metabolic syndrome components and variants in nine genes with inconsistent association with at least two metabolic syndrome components would predict future development of metabolic syndrome components. To this end, genetic variants were studied in a large prospective study including 16,143 nondiabetic subjects from the Malmö Preventive Project, with a mean follow-up period of 23 years. Logistic regression was used to calculate the risk of developing at least three metabolic syndrome components or the individual components. Both univariate and multivariate analyses revealed that polymorphisms in TCF7L2, FTO, WFS1 and IGF2BP2 predicted the development of at least three metabolic syndrome components. For TCF7L2, WFS1 and IGF2BP2, this could be accounted for by their association with hyperglycaemia, whereas in the case of FTO it was due to the association with obesity. None of the studied polymorphisms was associated with more than two metabolic syndrome components, whereas a composite genotype score of 17 SNPs associated with type 2 diabetes predicted the development of at least three metabolic syndrome components as well as hyperglycaemia. Polymorphisms in susceptibility genes for type 2 diabetes (TCF7L2, WFS1, IGF2BP2) and obesity (FTO) predispose to metabolic syndrome by increasing the risk of one specific metabolic syndrome component. These findings, therefore, argue against a unifying genetic component related to known candidate genes for the metabolic syndrome in Swedish subjects.
Abstract
