SNPs in apolipoprotein genes contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
BackgroundGenetic polymorphisms are known to affect fasting blood lipid levels, but their effects in the context of a high-fat meal challenge are less well characterized. This study investigates the association between SNPs in lipid transport genes and post-prandial blood lipid profiles in healthy adults in the U.S.
MethodsSubjects (n = 349) were 18-66 years of age and balanced by sex (48% male, 52% female). They had body-mass indices (BMI) ranging from 18.5 to 45.0 kg/m2 and completed the cross-sectional Nutritional Phenotyping Study. We assessed informative single nucleotide polymorphisms (SNPs) in five lipid transport genes (APOA5, APOB, APOC3, APOE, and LDLR). The association between serum lipid markers and genotypes was evaluated separately for each SNP using an analysis of variance (ANOVA) and pairwise interaction tests adjusted for sex, age, and BMI. Results Women carrying the C allele of rs3135506 in APOA5 and men carrying the C allele of rs429358 in APOE had reduced fasting and postprandial HDL-cholesterol levels. The C allele in APOE was also correlated with increased LDL-C. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive interactions were detected between APOA5 and APOE and between APOC3 and APOE risk alleles. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. Additionally, APOB (rs1042034) or LDLR (rs2228671) SNPs had no significant effect on serum triglyceride, cholesterol, or free fatty acid levels.
ConclusionsFasting and postprandial cholesterol levels are strongly correlated with APOA5, APOE, and APOC3 SNP genotypes in healthy adults. Sex increases the genetic impact of all tested SNPs on lipid profiles.