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Title: Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia

item WARODOMWICHIT, DARUNEEWAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ARNETT, DONNA - University Of Alabama
item KABAGAMBE, EDMOND - University Of Alabama
item TSAI, MICHAEL - University Of Minnesota
item HIXSON, JAMES - University Of Texas
item STRAKA, ROBERT - University Of Alabama
item PROVINCE, MICHAEL - Washington University School Of Medicine
item AN, PING - Washington University School Of Medicine
item Lai, Chao Qiang
item BORECKI, INGRID - Washington University School Of Medicine
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2008
Publication Date: 3/1/2009
Citation: Warodomwichit, D., Arnett, D.K., Kabagambe, E.K., Tsai, M.Y., Hixson, J.E., Straka, R.J., Province, M., An, P., Lai, C., Borecki, I., Ordovas, J. 2009. Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia. Journal of Nutrition. 139:439-446.

Interpretive Summary: The metabolic syndrome is a group of risk factors that include too much fat around the waist, elevated blood pressure, impaired fasting glucose, high triglyceride and low HDL-C (good cholesterol) levels. It increases the chance of developing heart disease and other health problems such as diabetes and stroke. Genetic and environmental factors play a role in development of metabolic syndrome. The current study observed that the mutation at the TCF7L2 gene (rs7903146) was related to increased risk of metabolic syndrome, primarily through lower risk of hypertriglyceridemia. Moreover, researchers also observed that its association with lipid profiles both fasting and after eating were modified by dietary fatty acids. The carriers of the mutation allele who had high intake of a certain type of polyunsaturated fatty acids (PUFA) called omega-6 PUFA were more likely to have a higher lipid which may contribute to metabolic syndrome or cardiovascular disease. However, the negative effect of the lipid profiles was not observed for omega-3 PUFA (fish oils). The findings support the genetic susceptibility for metabolic syndrome and the importance of gene and diet interaction.

Technical Abstract: The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk and it may exert its effect through metabolic syndrome (MetS) related traits and subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits, and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Carriers of the minor T allele at the C/T rs7903146 SNP had significantly higher fasting plasma glucose (P=0.012), lower HOMA-B (P=0.041), higher plasma VLDL (P=0.035) and lower large LDL particle (P=0.007) concentrations, and higher risk of MetS (P=0.011) than did CC individuals. Moreover, we identified significant interactions between this SNP and Polyunsaturated fatty acids (PUFA) intake modulating fasting VLDL particle concentrations (P=0.016), and postprandial TG (P=0.028), chylomicrons (P=0.025), total VLDL (P=0.026) and large VLDL (P=0.018) concentrations. Thus, only T allele carriers with PUFA intake > 7.36% of energy had elevated fasting plasma VLDL concentrations, and postprandial triglyceride rich lipoproteins. These variables did not differ between T allele carriers and non-carriers in the low PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes and cardiovascular disease.