Gene-nutrient interactions with dietary fat modulate the association between genetic variation of the ACSL1 gene and metabolic syndrome.
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.
Phillips
Catherine M
CM
Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, and Institute of Food and Health, University College Dublin, Ireland.
Goumidi
Louisa
L
Bertrais
Sandrine
S
Field
Martyn R
MR
Cupples
L Adrienne
LA
Ordovas
Jose M
JM
Defoort
Catherine
C
Lovegrove
Julie A
JA
Drevon
Christian A
CA
Gibney
Michael J
MJ
Blaak
Ellen E
EE
Kiec-Wilk
Beata
B
Karlstrom
Britta
B
Lopez-Miranda
Jose
J
McManus
Ross
R
Hercberg
Serge
S
Lairon
Denis
D
Planells
Richard
R
Roche
Helen M
HM
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
D015415:Biomarkers; D004041:Dietary Fats; D005227:Fatty Acids; D007527:Isoenzymes; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase