Comprehensive Evaluation of the Association of APOE Genetic Variation with Plasma Lipoprotein Traits in U.S. Whites and African Blacks
Open accessAbstract
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.
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In the Zaheda 2014 study, there was no association between p.Leu46Pro and TG levels in subjects from US and African populations.
“In particular, in the Zaheda 2014 study, there was no association between p.Leu46Pro and TG levels in subjects from US and African populations [49].”
From Spectrum and Prevalence of Rare APOE Variants and Their Association with Familial Dysbetalipoproteinemia (2024) · cites this paper as [49]
In Results, Table 1 (page unavailable), p.Leu46Pro is listed as APOE3106/rs769452 and shows no statistically significant association with TG in U.S. non-Hispanic Whites (adjusted p = 0.2544). Table 2 reports results for African Blacks but does not list this variant, so the claimed lack of association in that population is not established. (LLM, conf=0.88)
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- Authors
- Radwan, Z. H., Wang, X., Waqar, F., Pirim, D., Niemsiri, V., Hokanson, J. E., Hamman, R. F., Bunker, C. H., Barmada, M. M., Demirci, F. Y., & Kamboh, M. I.
- Affiliations
- University of Pittsburgh (US)
- Colorado School of Public Health (US)
- Corresponding author
- Kamboh, M. Ilyas
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-12-12
- Volume
- 9
- Issue
- 12
- Pages
- e114618
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4264772
- OpenAlex
- W2094720661
- Cited by
- 27
- References
- 51
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 3
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
- Bursa Uludag University - AVESIS (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (UL1TR001425)
- National Heart, Lung, and Blood Institute (HL084613, R01HL084613)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- APOE gene, serum lipoproteins, HDL cholesterol, triglycerides, LDL cholesterol, APOE ε4, novel sequence variants, tag SNPs, genotype-phenotype correlation, Black Africans, non-Hispanic whites, lipid traits
- MeSH terms
- Apolipoproteins E, Black or African American, Female, Haplotypes, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Phenotype, Triglycerides, United States, Polymorphism, Single Nucleotide, Black People, White People, Genetic Association Studies, Molecular Sequence Annotation
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