title: Dietary saturated fat, gender and genetic variation at the TCF7L2 locus predict the development of metabolic syndrome.
abstract: 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<.05) compared to the CC homozygotes. Metabolic syndrome risk was also modulated by dietary saturated fat (SFA) intake (P=.035 for interaction). High dietary SFA intake (≥15.5% energy) exacerbated MetS risk (OR 2.35, 95% CI 1.29-4.27, P=.005) and was associated with further impaired insulin sensitivity in the T allele carriers relative to the CC homozygotes (P=.025) and particularly to the T allele carriers with the lowest SFA intake (P=.008). No significant genotype effect on MetS risk or insulin sensitivity was evident among low-SFA consumers. In conclusion, the TCF7L2 rs7903146 polymorphism influences MetS risk, which is augmented by both gender and dietary SFA intake, suggesting novel gene-diet-gender interactions.
authors.affiliation: Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phillips
authors.forename: Louisa
authors.initials: L
authors.lastname: Goumidi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bertrais
authors.forename: Martyn R
authors.initials: MR
authors.lastname: Field
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Denis
authors.initials: D
authors.lastname: Lairon
authors.forename: Richard
authors.initials: R
authors.lastname: Planells
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D004247:DNA