Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: from the LIPGENE study

Delgado-Lista, J., Perez-Martinez, P., Philips, C. M., Williams, C. M., Gulseth, H. L., Helal, O., Blaak, E. E., Kiec-Wilk, B., Basu, S., Drevon, C. A., Defoort, C., Saris, W. H., Wybranska, I., Riserus, U., Lovegrove, J. A. ORCID: https://orcid.org/0000-0001-7633-9455, Roche, H. M., Lopez-Miranda, J. and Garcia-Rios, A. (2011) Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: from the LIPGENE study. Atherosclerosis, 214 (1). pp. 110-116. ISSN 0021-9150 doi: 10.1016/j.atherosclerosis.2010.10.027

Abstract/Summary

Aims/hypothesis: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). Methods: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. Results: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. Conclusions/interpretation: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/17888
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Metabolic syndrome; Wnt; TCF7L2; Insulin secretion; Insulin resistance; Blood pressure; Lipids; Saturated fatty acids; LIPGENE
Publisher	Elsevier
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