title: APOA5 gene variation interacts with dietary fat intake to modulate obesity and circulating triglycerides in a Mediterranean population.
abstract: APOA5 is one of the strongest regulators of plasma TG concentrations; nevertheless, its mechanisms of action are poorly characterized. Genetic variability at the APOA5 locus has also been associated with increased cardiovascular disease risk; however, this predisposition could be attenuated in the context of a prudent diet as traditionally consumed in the Mediterranean countries. We have investigated the interaction between a single nucleotide polymorphism (SNP) at the APOA5 gene (-1131T > C) and dietary fat that may modulate TG-rich lipoprotein concentrations and anthropometric measures in overweight and obese participants. We recruited 1465 participants from a Spanish population (20-65 y old; BMI 25-40 kg/m(2)) attending outpatient obesity clinics. Consistent with previous reports, we found an association between the APOA5-1131T > C SNP and TG-rich lipoprotein concentrations that were higher in carriers of the minor allele than in noncarriers (P < 0.001). Moreover, we found a significant genotype-dietary fat interaction for obesity traits. Participants homozygous for the -1131T major allele had a positive association between fat intake and obesity, whereas in those carrying the APOA5-1131C minor allele, higher fat intakes were not associated with higher BMI. Likewise, we found genotype-dietary fat interactions for TG-rich lipoproteins (P < 0.001). In conclusion, we have replicated previous gene-diet interactions between APOA5 -1131T > C SNP and fat intake for obesity traits and detected a novel interaction for TG-rich lipoprotein concentrations. Our data support the hypothesis that the minor C-allele may protect those consuming a high-fat diet from obesity and elevated concentrations of TG-rich lipoproteins.
authors.affiliation: Department of Physiology, University of Murcia, Campus de Espinardo, s/n. 30100, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez-Moreno
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Juan C
authors.initials: JC
authors.lastname: Baraza
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.forename: Marta
authors.initials: M
authors.lastname: Garaulet
mesh_terms: D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D019083:Mediterranean Region; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D050177:Overweight / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood; D055815:Young Adult
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D004041:Dietary Fats; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030087:lipoprotein triglyceride