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

C.M. Phillips, L. Goumidi, S. Bertrais, M.R. Field, L.A. Cupples, J.M. Ordovas, J. McMonagle, C. Defoort, J.A. Lovegrove, C.A. Drevon, E.E. Blaak, B. Kiec Wilk, U. Riserus, J. Lopez Miranda, R. McManus, S. Hercberg, D. Lairon, R. Planells, H.M. Roche

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Abstract

Acetyl-CoA carboxylase beta (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.jlr In conclusion, the ACC2 rs4766587 polymorphism influences MetS risk, which was modulated by dietary fat, suggesting novel gene-nutrient interactions.-Phillips, C. M., L. Goumidi, S. Bertrais, M. R. Field, L. Adrienne Cupples, J. M. Ordovas, J. McMonagle, C. Defoort, J. A. Lovegrove, C. A. Drevon, E. E. Blaak, B. Kiec-Wilk, U. Riserus, J. Lopez-Miranda, R. McManus, S. Hercberg, D. Lairon, R. Planells, and H. M. Roche. ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat. J. Lipid Res. 2010. 51: 3500-3507.

Original languageEnglish
Pages (from-to)3500-3507
Number of pages8
JournalJournal of Lipid Research
Volume51
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • genetic polymorphisms
  • insulin resistance
  • fatty acid metabolism
  • polyunsaturated fatty acids
  • ACETYL-COA CARBOXYLASE
  • ELEMENT-BINDING PROTEIN-1
  • SKELETAL-MUSCLE
  • INSULIN-RESISTANCE
  • ACID-COMPOSITION
  • LIPOGENIC GENES
  • SERUM-LIPIDS
  • ASSOCIATION
  • EXPRESSION
  • GLUCOSE

Cite this

Phillips, C. M., Goumidi, L., Bertrais, S., Field, M. R., Cupples, L. A., Ordovas, J. M., McMonagle, J., Defoort, C., Lovegrove, J. A., Drevon, C. A., Blaak, E. E., Kiec Wilk, B., Riserus, U., Lopez Miranda, J., McManus, R., Hercberg, S., Lairon, D., Planells, R., & Roche, H. M. (2010). ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat. Journal of Lipid Research, 51(12), 3500-3507. https://doi.org/10.1194/jlr.M008474