title: Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome.
abstract: Long-chain acyl CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and triacylglycerol (TAG) synthesis. Disturbance of these pathways may result in dyslipidemia and insulin resistance, hallmarks of the metabolic syndrome (MetS). Dietary fat is a key environmental factor that may interact with genetic determinants of lipid metabolism to affect MetS risk. We investigated the relationship between ACSL1 polymorphisms (rs4862417, rs6552828, rs13120078, rs9997745, and rs12503643) and MetS risk and determined potential interactions with dietary fat in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1,754). GG homozygotes for rs9997745 had increased MetS risk {odds ratio (OR) 1.90 [confidence interval (CI) 1.15, 3.13]; P = 0.01}, displayed elevated fasting glucose (P = 0.001) and insulin concentrations (P = 0.002) and increased insulin resistance (P = 0.03) relative to the A allele carriers. MetS risk was modulated by dietary fat, whereby the risk conferred by GG homozygosity was abolished among individuals consuming either a low-fat (<35% energy) or a high-PUFA diet (>5.5% energy). In conclusion, ACSL1 rs9997745 influences MetS risk, most likely via disturbances in fatty acid metabolism, which was modulated by dietary fat consumption, particularly PUFA intake, suggesting novel gene-nutrient interactions.
authors.affiliation: Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, and Institute of Food and Health, University College 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: 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: Michael J
authors.initials: MJ
authors.lastname: Gibney
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Britta
authors.initials: B
authors.lastname: Karlstrom
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: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000235:genetics*; D004041:Dietary Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005502:Food; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D054647:Nutrigenomics; D011110:Polymorphism, Genetic; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D007527:Isoenzymes; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase