Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol

Abstract

Toll-like receptor 4 (TLR4) is a protein of the innate immune system hypothesized to mediate some of the effects of a high-fat diet on inflammation and insulin resistance. As both these factors are associated with the metabolic syndrome (MetS), genetic variation in TLR4 may affect the relationship between dietary lipids and MetS. The objective of the study was to determine whether 2 polymorphisms in TLR4 (rs4986790 Asp299Gly and rs5030728 G>A) modify the relationship between dietary fat and markers of the MetS. Participants were healthy young men and women of various ethnocultural backgrounds. Dietary intake was estimated using a 1-month semiquantitative food frequency questionnaire, and fasting blood samples were taken for genotyping and biomarker measurement. The Asp299Gly polymorphism in TLR4 was associated with increased insulin, homeostasis model assessment of insulin resistance (P