ArticlePloS one2012
Cholesteryl Ester Transfer Protein (CETP) polymorphisms affect mRNA splicing, HDL levels, and sex-dependent cardiovascular risk.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.Journal of medical genetics · 2016Pooled it
- Weight gain prevention buffers the impact of CETP rs3764261 on high density lipoprotein cholesterol in young adulthood: The Study of Novel Approaches to Weight Gain Prevention (SNAP).Nutrition, metabolism, and cardiovascular diseases : NMCD · 2018Trial
- CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials.Journal of lipid research · 2015Trial
- Targeting PCSK9, APOB, and CETP at the Transcriptome Level by hsa-miR-30b-3p Reduces LDL-Associated Protein in Huh-7 Cells.Molecular biology reports · 2026Article
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia.Journal of atherosclerosis and thrombosis · 2025Review
- Healthier Lipid Profiles of Japanese Adults, Especially in Women with Elevated High-Density Lipoprotein Cholesterol (HDL-C), Are Associated with Low HDL-C Peroxide Content.Antioxidants (Basel, Switzerland) · 2024Article
- CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Roles of peripheral lipoproteins and cholesteryl ester transfer protein in the vascular contributions to cognitive impairment and dementia.Molecular neurodegeneration · 2023Review
- Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis.Frontiers in cardiovascular medicine · 2023Review
- A Nutrigenetic Update on CETP Gene-Diet Interactions on Lipid-Related Outcomes.Current atherosclerosis reports · 2022Review
- Review
- Relationship between high-density lipoprotein cholesterol levels and endothelial function in women: a cross-sectional study.BMJ open · 2020Article
- Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants atBiomolecules · 2019Article
- Identifying genetic markers associated with susceptibility to cardiovascular diseases.Future science OA · 2019Review
- Relationship between CETP gene polymorphisms with coronary artery disease in Polish population.Molecular biology reports · 2018Article
- Interactions Between Regulatory Variants in CYP7A1 (Cholesterol 7α-Hydroxylase) Promoter and Enhancer Regions Regulate CYP7A1 Expression.Circulation. Genomic and precision medicine · 2018Article
- Article
- Article
- Association between Six CETP Polymorphisms and Metabolic Syndrome in Uyghur Adults from Xinjiang, China.International journal of environmental research and public health · 2017Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Polymorphisms in and around the Cholesteryl Ester Transfer Protein (CETP) gene have been associated with HDL levels, risk for coronary artery disease (CAD), and response to therapy. The mechanism of action of these polymorphisms has yet to be defined. We used mRNA allelic expression and splice isoform measurements in human liver tissues to identify the genetic variants affecting CETP levels. Allelic CETP mRNA expression ratios in 56 human livers were strongly associated with several variants 2.5-7 kb upstream of the transcription start site (e.g., rs247616 p = 6.4 × 10(-5), allele frequency 33%). In addition, a common alternatively spliced CETP isoform lacking exon 9 (Δ9), has been shown to prevent CETP secretion in a dominant-negative manner. The Δ 9 expression ranged from 10 to 48% of total CETP mRNA in 94 livers. Increased formation of this isoform was exclusively associated with an exon 9 polymorphism rs5883-C>T (p = 6.8 × 10(-10)) and intron 8 polymorphism rs9930761-T>C (5.6 × 10(-8)) (in high linkage disequilibrium with allele frequencies 6-7%). rs9930761 changes a key splicing branch point nucleotide in intron 8, while rs5883 alters an exonic splicing enhancer sequence in exon 9.The effect of these polymorphisms was evaluated in two clinical studies. In the Whitehall II study of 4745 subjects, both rs247616 and rs5883T/rs9930761C were independently associated with increased HDL-C levels in males with similar effect size (rs247616 p = 9.6 × 10(-28) and rs5883 p = 8.6 × 10(-10), adjusted for rs247616). In an independent multiethnic US cohort of hypertensive subjects with CAD (INVEST-GENE), rs5883T/rs9930761C alone were significantly associated with increased incidence of MI, stroke, and all-cause mortality in males (rs5883: OR 2.36 (CI 1.29-4.30), p = 0.005, n = 866). These variants did not reach significance in females in either study. Similar to earlier results linking low CETP activity with poor outcomes in males, our results suggest genetic, sex-dependent CETP splicing effects on cardiovascular risk by a mechanism independent of circulating HDL-C levels.
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Registered trials
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