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.

Conflict of interest statement

Author disclosures: C. Sánchez-Moreno, J. M. Ordovás, C. Smith, J. C. Baraza, Y. C. Lee, and M. Garaulet, no conflicts of interest.

Figures

FIGURE 1

Plasma VLDL (A) and TG (B) concentrations in Spanish adults who attended 5 outpatient obesity clinics by APOA5-1131T > C SNP and by fat intake greater or less than the mean of 98 g/d. Values are means ± SEM, n = (46–337). Data were log transformed before analysis. Means without a common letter differ, *P < 0.001. Estimated means were adjusted for sex, age, tobacco smoking, regular alcohol consumption, and nutrition center. P-interactions between fat intake and the SNP (P < 0.001) were obtained with the multivariate interaction model containing fat intake as a categorical variable and the APOA5 SNP and additional control for the other covariates.

FIGURE 2

Predicted plasma TG concentrations in Spanish adults who attended 5 outpatient obesity clinics by the APOA5–1131T > C SNP depending on the total fat consumed (as a continuous variable); n = 1296 genotyped participants *(P = 0.0011). P-interaction = 0.003. Predicted values were calculated from the regression models containing the total fat intake, the APOA5–1131T > C SNP, the interaction term, and the potential confounders for sex, age, tobacco smoking, regular alcohol consumption, and nutrition center.