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ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat.

Phillips , C. M., Goumidi , L., Bertrais , S., Field , M. R., Cupples , L. A., Ordovas , J. M., McMonagle , J., Defoort , C., Lovegrove, J. A. ORCID: https://orcid.org/0000-0001-7633-9455, Drevon , C. A., Blaak , E. E., Kiec-Wilk , B., Riserus , U., Lopez-Miranda , J., McManus , R., Hercberg , S., Lairon, D., Planells , R. and Roche , H. M. (2010) ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat. Journal of Lipid Research, 51 (12). pp. 3500-3507. ISSN 1539-7262

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To link to this item DOI: 10.1194/jlr.M008474

Abstract/Summary

Acetyl-CoA carboxylase β (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. Disturbance of these pathways is associated with impaired insulin responsiveness and metabolic syndrome (MetS). Gene-nutrient interactions may affect MetS risk. This study determined the relationship between ACC2 polymorphisms (rs2075263, rs2268387, rs2284685, rs2284689, rs2300453, rs3742023, rs3742026, rs4766587, and rs6606697) and MetS risk, and whether dietary fatty acids modulate this in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). Minor A allele carriers of rs4766587 had increased MetS risk (OR 1.29 [CI 1.08, 1.58], P = 0.0064) compared with the GG homozygotes, which may in part be explained by their increased body mass index (BMI), abdominal obesity, and impaired insulin sensitivity (P < 0.05). MetS risk was modulated by dietary fat intake (P = 0.04 for gene-nutrient interaction), where risk conferred by the A allele was exacerbated among individuals with a high-fat intake (>35% energy) (OR 1.62 [CI 1.05, 2.50], P = 0.027), particularly a high intake (>5.5% energy) of n-6 polyunsaturated fat (PUFA) (OR 1.82 [CI 1.14, 2.94], P = 0.01; P = 0.05 for gene-nutrient interaction). Saturated and monounsaturated fat intake did not modulate MetS risk. Importantly, we replicated some of these findings in an independent cohort. In conclusion, the ACC2 rs4766587 polymorphism influences MetS risk, which was modulated by dietary fat, suggesting novel gene-nutrient interactions.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
ID Code:15666
Publisher:American Society for Biochemistry and Molecular Biology

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