Interaction between the APOC3 gene promoter polymorphisms, saturated fat intake and plasma lipoproteins

Objective: To test the hypothesis that APOC3 gene polymorphisms modulate the effect of saturated fat (SAT) intake on plasma lipoproteins and LDL size. Methods: We studied 336 randomly selected residents from Costa Rica. APOC3 polymorphisms were genotyped in the promoter region (T-455C, T-625del) and the C3238G 3′ untranslated region (UTR). Dietary intake was assessed by a validated food-frequency questionnaire (FFQ) and median saturated fat intake (11%) was used to define low and high exposure to saturated fat. Results: Allele frequencies were 0.49, 0.51 and 0.19 for the APOC3-455C, -625de1, and APOC3 3238G alleles, respectively. Significant gene–diet interactions were found for total (P<0.0004) and LDL cholesterol (P<0.01). In homozygotes for the APOC3-455T-625T alleles, saturated fat intake was associated with a 13% increase in total cholesterol (P<0.001) and a 20% increase in LDL cholesterol (P<0.001). In contrast, no association between plasma lipoproteins and saturated fat intake was found among carriers of the APOC3-455C-625del allele. The APOC3 3238G UTR allele did not modify the observed association. Conclusion: Compared to a diet high in saturated fat, a habitually low saturated fat diet is associated with a beneficial lipoprotein profile only among homozygotes of the APOC3 promoter 455T-625T polymorphism.