Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults

Abstract

The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, andMetSrisk andwhether plasma fatty acids, a biomarker of dietary fatty acids,modulate this. LEPRpolymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study ofMetS cases andmatched controls (n = 1754). LEPR rs3790433 GG homozygotes had increasedMetS risk compared with theminor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05-2.57; P = 0.028], whichmay be accounted for by their increased risk of elevated insulin concentrations (OR 2.40;95% CI: 1.28-4.50; P = 0.006) and insulin resistance (OR= 2.15; 95% CI: 1.18-3.90; P = 0.012). Low (less thanmedian) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92-2.94) and insulin resistance (OR 3.40-3.47). Interestingly, these associationswere abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for theLEPRrs3790433Gallelewasassociatedwith insulin resistance,whichmaypredispose to increasedMetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA. © 2010 American Society for Nutrition.