Abstract 10412: Calpain-10 Genetic Variants Interact with Plasma Saturated Fatty Acid Levels to Influence Insulin Resistance in Patients with Metabolic Syndrome
Introduction: Calpain-10 protein may play a role in glucose metabolism, pancreatic beta-cell insulin secretion and regulating thermogenesis. Several CAPN10 polymorphic sites have been studied for their potential use as markers for type 2 diabetes mellitus and metabolic syndrome (MetS). Dietary fat is a key environmental factor, which may interact with genetic factors to affect glucose metabolism. Hypothesis: We hypothesized that genetic variations affecting the activity and/or expression of calpain-10 in humans could be associated with variability in insulin response to dietary fat. Thus, our aim was to examine whether the genetic variability at the CAPN10 gene locus is associated with the degree of insulin resistance to dietary plasma fatty acid in MetS patients.
Methods: Insulin sensitivity (HOMA-IR, glucose sensitivity, insulin sensitivity index), insulin secretion (disposition index, acute insulin response, HOMA-B), plasma fatty acid composition and five CALPN10 SNPs were determined in a cross-sectional analysis of 430 patients with MetS participating in the LIPGENE dietary intervention cohort (NCT00429195).
Results: Gene-nutrient interactions were detected. In the whole cohort, the rs2953171 SNP interacted with plasma saturated fatty acids (SFA) to significantly associate with insulin resistance. Among subjects with low SFA consumption (below the median), the minor A allele was associated with higher fasting insulin concentration (P<0.031) and HOMA-IR (P<0.028), and lower glucose sensitivity (P<0.013) compared with the GG genotype. In contrast, subjects carrying the A allele with the highest consumption of SFA (above the median) showed lower fasting insulin and HOMA-IR, and higher glucose sensitivity compared with the GG genotype. There were no significant interactions between other plasma fatty acid variables and CAPN10 SNPs on glucose metabolism.
Conclusions: This study supports that certain polymorphism at the CAPN10 gene locus may influence insulin resistance by interacting with plasma fatty acid composition in MetS patients. Further investigation of these novel associations and gene-nutrient interactions may help to improve therapeutic efficacy of dietary recommendations with a ‘personalised nutrition’ approach.
- © 2010 by American Heart Association, Inc.