ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat.
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.
Phillips
Catherine M
CM
Nutrigenomics Research Group, UCD School of Public Health and Population Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Goumidi
Louisa
L
Bertrais
Sandrine
S
Field
Martyn R
MR
Cupples
L Adrienne
LA
Ordovas
Jose M
JM
McMonagle
Jolene
J
Defoort
Catherine
C
Lovegrove
Julie A
JA
Drevon
Christian A
CA
Blaak
Ellen E
EE
Kiec-Wilk
Beata
B
Riserus
Ulf
U
Lopez-Miranda
Jose
J
McManus
Ross
R
Hercberg
Serge
S
Lairon
Denis
D
Planells
Richard
R
Roche
Helen M
HM
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
D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D000103:Acetyl-CoA Carboxylase