title: ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat.
abstract: 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.
authors.affiliation: Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, 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: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Jolene
authors.initials: J
authors.lastname: McMonagle
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Ulf
authors.initials: U
authors.lastname: Riserus
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
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: D000103:Acetyl-CoA Carboxylase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000483:Alleles; D015992:Body Mass Index; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism*; D056128:Obesity, Abdominal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D000103:Acetyl-CoA Carboxylase