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Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study
Open accessAbstract
Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; -1131T>C, -3A>G, 56C>G IVS3+ 476G>A, and 1259T>C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C>G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population. SNP analyses revealed that the -1131T>C and 56C>G SNPs were significantly associated with higher plasma TG concentrations in both men and women. For RLP and lipoprotein subclasses, we observed gender-specific association for the -1131T>C and 56C>G SNPs. Female carriers of the -1131C allele had higher RLP concentrations, whereas in males, significant associations for RLPs were observed for the 56G allele. Moreover, haplotype analyses confirmed these findings and revealed that the 22122 and 11211 haplotypes exhibited different associations with HDL cholesterol concentrations. In women, the -1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03-3.34; P = 0.04), in agreement with the association of this SNP with higher RLPs.
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“The minor allele of rs3135506 (minor allele frequency (MAF) of about 6% in whites) has been repeatedly associated with increased plasma TG concentrations [96–99].”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [97]
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Metadata
- Authors
- Lai, C.-Q., Demissie, S., Cupples, L. A., Zhu, Y., Adiconis, X., Parnell, L. D., Corella, D., & Ordovas, J. M.
- Affiliations
- Tufts University (US)
- Boston University (US)
- Corresponding author
- Lai, Chao-Qiang
- ORCID
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 45
- Issue
- 11
- Pages
- 2096-2105
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2154292243
- Cited by
- 163
- References
- 59
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 1 · 2012: 11
- FWCI
- 9.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Heart, Lung, and Blood Institute (HL54776, R01HL054776)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- APOA5, apolipoprotein A-I, single nucleotide polymorphisms, plasma triglycerides, remnant-like particles, lipoprotein subclasses, cardiovascular risk, HDL cholesterol, haplotypes, linkage disequilibrium, sex differences, Framingham Heart Study
- MeSH terms
- Apolipoprotein A-V, Adult, Aged, Alleles, Apolipoproteins, Apolipoproteins A, Cardiovascular Diseases, Cardiovascular System, Cholesterol, Coronary Disease, Female, Genotype, Haplotypes, Humans, Lipoproteins, Male, Middle Aged, Polymorphism, Genetic, Risk, Sex Factors, Triglycerides, Genetic Variation, Linkage Disequilibrium, Polymorphism, Single Nucleotide
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