Comprehensive Evaluation of the Association of APOE Genetic Variation with Plasma Lipoprotein Traits in U.S. Whites and African Blacks

Abstract

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE*2 and APOE*4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol.

ApoE rs429358 and rs7412 Polymorphism and Gender Differences of Serum Lipid Profile and Cognition in Aging Chinese Population

“…Adults carrying the T allele of ApoE rs7412 demonstrated lower serum LDL-C levels. This result is consistent with previously reported studies (Bennet et al, 2010 ; Barbosa et al, 2012 ; Radwan et al, 2014 ). However, few studies have explored the impact(s) of ApoE polymorphism on plasma high-density lipoprotein (HDL-C) and triglycerides (TG) levels.…”

“…The knowledge of the role of ApoE genetic polymorphism in affecting different individual variations with plasma cholesterol especially, low-density lipoproteins (LDL-C) levels in the general population is also well established (Bennet et al, 2007 ; Willer et al, 2008 ). Radwan et al's study indicates that ApoE rs429358 and ApoE rs7412 polymorphism are significantly associated with plasma LDL-C levels (Radwan et al, 2014 ). In this present study, findings of significant statistical associations between genetic variation in ApoE rs7412 and serum LDL-C levels was established.…”

Investigating the GWAS-Implicated Loci for Rheumatoid Arthritis in the Pakistani Population

“…The Benjamin Hochberg false discovery rate (FDR) was applied to correct for multiple testing [20]. p < 0:05 was considered as suggestive evidence of association and FDR (q value) of <0.20 as statistically significant as used in previous reports [21,22]. All analyses were implemented in R, version 3.4.4.…”

Apolipoprotein E gene polymorphism modifies fasting total cholesterol concentrations in response to replacement of dietary saturated with monounsaturated fatty acids in adults at moderate cardiovascular disease risk

“…The effect of genetic variations of APOE on lipid concentrations (i.e. LDL-C) [ 20 – 23 ] and the effect of the APOE polymorphisms on the circulating lipid response to dietary fat (i.e. SFA and MUFA) have been previously demonstrated; however, the findings have been inconsistent [ 24 – 26 ].…”