ArticleMolecular medicine (Cambridge, Mass.)
APOE/C1/C4/C2 gene cluster genotypes, haplotypes and lipid levels in prospective coronary heart disease risk among UK healthy men.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 4 of them syntheses that pooled it.
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Who cites it
32 citing papers in PubMed, 4 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review.Cardiovascular diabetology · 2022Pooled it
- Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies.American heart journal · 2016Pooled it
- Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta-Analysis.BioMed research international · 2016Pooled it
- Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.Nature communications · 2014Pooled it
- Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.European heart journal · 2013Trial
- Plasma proteomic profiling of septic shock and acute pancreatitis identifies shared signatures and disease-specific pathways.Scientific reports · 2026Article
- Association of APOC2 upstream variant rs10425530 with BMI predicted to overlap with NR2C2, GCM2 and NR2C1 binding sites.Human genomics · 2026Article
- The genetic landscape of human functional brain connectivity.Nature communications · 2026Article
- Partitioning and aggregating cross-tissue and tissue-specific genetic effects to identify gene-trait associations.Nature communications · 2024Article
- Sequence Variant Analysis of theInternational journal of molecular sciences · 2023Article
- Autoimmune Reaction Associated With Long COVID Syndrome and Cardiovascular Disease: A Genetic Case Report.JACC. Case reports · 2023Article
- Loss of FOXA2 induces ER stress and hepatic steatosis and alters developmental gene expression in human iPSC-derived hepatocytes.Cell death & disease · 2022Article
- Genetic Variants at theGenes · 2022Article
- Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond.International journal of molecular sciences · 2019Review
- Article
- Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors.Lipids in health and disease · 2018Article
- Joint analysis of multiple blood pressure phenotypes in GAW19 data by using a multivariate rare-variant association test.BMC proceedings · 2016Article
- The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.Lipids in health and disease · 2015Article
- Genetic Contribution of Variants near SORT1 and APOE on LDL Cholesterol Independent of Obesity in Children.PloS one · 2015Article
- Analysis of the placental tissue transcriptome of normal and preeclampsia complicated pregnancies.Acta naturae · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The role of common APOE variants on plasma lipids, particularly low density lipoprotein (LDL) levels, and coronary heart disease (CHD) risk is well known; the influence of variation in the other nearby apolipoprotein genes APOC1, APOC4 and APOC2 is unclear. This study examines the association between APOE/C1/C4/C2 gene cluster variation using tagging SNPs and plasma lipid concentration along with risk of CHD in a prospective cohort. Genotypes for 11 common APOE/C1/C4/C2 SNPs were determined in 2,767 middle-aged (49 to 64 years) men from the Second Northwick Park Heart Study, with 275 CHD events over a 15-year follow-up period. Seven SNPs showed significant associations with one or more lipid trait in univariate analysis. Multivariate and haplotype analysis showed that the APOE genotypes are most strongly associated with effects on LDL-C and apoB concentration (explaining 3.4% of the LDL-C variance) while the other SNPs in this gene cluster explained an additional 1.2%. Haplotypes in APOC2 and APOC4 were associated with modest effects on HDL-C and apoAI (explaining respectively 1.4% and 1.2%). Carriers of the APOE ɛ2 SNP had a significantly lower risk of CHD hazard ratio (HR) of 0.63 (95% confidence interval [CI]: 0.42-0.95), as did carriers of the APOC2 SNP rs5127 (HR = 0.72, 95% CI: 0.56-0.93), while carriers of APOC1 SNP rs4803770 had higher risk of CHD (HR = 1.36, 95% CI: 1.04-1.78) compared with noncarriers. While the common APOE polymorphism explains the majority of the locus genetic determinants of plasma lipid levels, additional SNPs in the APOC1/C2 region may contribute to CHD risk, but these effects require confirmation.
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