SNPs in Apolipoproteins Contribute to Sex-Dependent Differences in Blood Lipids Before and After A Dietary Challenge in Healthy U.S. Adults

Abstract

Background The effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid levels in healthy adults in the U.S. Methods Men and women (n = 393) between 18-66 years of age with BMIs ranging from 18.5-45 kg/m 2 completed the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men = 167, 48%; women = 182, 52%) gave consent for genotyping. SNPs in APOA5 , APOB , APOC3 , APOE , and LDLR were assessed. Results Reduced blood HDL-cholesterol levels were associated with the C allele of the APOA5 SNP (rs3135506) in women and the C allele of the APOE SNP (rs429358) in men in both fasting and postprandial states. The C allele of the APOE SNP was also correlated with increased LDL-C levels. The APOC3 rs2854116 TT genotype was associated with elevated total cholesterol in both sexes. Nevertheless, these SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. Additionally, no significant effects of SNPs in APOB (rs1042034) and LDLR (rs2228671) on triglycerides, cholesterol, or non-esterified free fatty acids levels were found. Conclusions Cholesterol levels are strongly correlated with genotypes of the tested SNPs in APOA5 and APOE in a sex-dependent manner during fasting and postprandial states of healthy adults. Trial registration: ClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287.