Dietary saturated fat, gender and genetic variation at the TCF7L2 locus predict the development of metabolic syndrome

Transcription factor 7-like 2 (TCF7L2) is the strongest genetic determinant of type 2 diabetes (T2DM) and insulin-related phenotypes to date. Dietary fat is a key environmental factor which may interact with genotype to affect risk of metabolic syndrome (MetS) and T2DM. This study investigated the relationship between the TCF7L2 rs7903146 polymorphism, insulin sensitivity/resistance and MetS in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n=1754) and determined potential interactions with dietary fat intake. Female minor T allele carriers of rs7903146 had increased MetS risk (odds ratio [OR] 1.66, confidence interval [CI] 1.02–2.70, P=.04) and displayed elevated insulin concentrations (P=.005), impaired insulin sensitivity (P=.011), increased abdominal obesity (P=.008) and body mass index (P=.001) and higher blood pressure (P