Circulating Cholesteryl Ester Transfer Protein and Coronary Heart Disease: Mendelian Randomization Meta-Analysis
Abstract
Background—: The cholesteryl ester transfer protein (CETP) plays a central role in reverse cholesterol transport. Currently, it remains unresolved whether circulating CETP is causally associated with coronary heart disease (CHD). We aimed to investigate this causal association using CETP gene rs708272 polymorphism as an instrument in a Mendelian randomization meta-analysis. Methods and Results—: We searched PubMed and EMBASE before May 2014. Data and study quality were assessed in duplicate. Thirty-four articles (17 813 CHD patients and 22 203 controls) were qualified. Overall analyses revealed a significant association of rs708272-B1 allele with a reduced CHD risk compared with B2 allele under allelic (odds ratio and 95% confidence interval: 0.87 and 0.82–0.92; P <0.001), homozygous genotypic (0.74 and 0.66–0.83; P <0.001), and dominant (0.87 and 0.80–0.94; P <0.001) models. Carriers of rs708272-B1B1 genotype (weighted mean difference and 95% confidence interval: −0.21 and −0.41 to 0.00 μg/dL; P =0.052) or B1 allele (−0.15 and −0.30 to 0.00 μg/dL; P =0.056) had a marginally lower circulating CETP level compared with B2B2 genotype carriers. In Mendelian randomization analysis, there was a 25% (odds ratio and 95% confidence interval: 0.75 and 0.19–0.91) and a 17% (0.83 and 0.41–0.96) significantly reduced risk of CHD by a reduction of 0.2 μg/mL in circulating CETP for the comparison of B1B1 genotype and B1 allele with B2B2 genotype, respectively. There were low probabilities of publication bias. Conclusions—: Our findings demonstrate that the long-term genetically reduced circulating CETP might be causally associated with the low risk of CHD.
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Patients with genetically reduced CETP serum concentrations appear to have a slightly reduced risk of coronary heart disease.
“On the one hand, patients with genetically reduced CETP serum concentrations appear to have a slightly reduced risk of coronary heart disease [99–102].”
From HDL cholesterol: reappraisal of its clinical relevance (2017) · cites this paper as [102]
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Hallén, J., & Sreeharan, N. (2018) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvy029 · Cited by 7 · see citing works
Lin, S., Dai, R., & Lin, R. (2016) · Oncotarget · doi:10.18632/oncotarget.12898 · Cited by 6 · see citing works
Savla, J. J., & Neeland, I. J. (2018) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-018-0566-9 · Cited by 4 · see citing works
Translational and Therapeutic Approaches to the Understanding and Treatment of Dyslipidemia
Zhang, H., Vallim, T. Q. D. A., & Martel, C. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307808 · Cited by 4 · see citing works
Juliani, F. C., Freitas, F. R., Miname, M. H., Rocha, V. Z., Lima, J. M. D. H. S., Freitas, R. A. M. S., Damasceno, N. R. T., Krieger, J. E., Maranhão, R. C., & Santos, R. D. (2025) · Journal of clinical lipidology · doi:10.1016/j.jacl.2025.11.014 · Cited by 1 · see citing works
Rouland, A., Gautier, T., Denimal, D., Duvillard, L., Simoneau, I., Rageot, D., Vergès, B. L., & Bouillet, B. (2024) · Metabolites · doi:10.3390/metabo14090487 · Cited by 1 · see citing works
Sodium transport in frog skin: a student laboratory experiment in epithelial physiology.
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Lipoprotein Subfractions in Clinical Practice
Meeusen, J. W. (2020) · Contemporary cardiology · doi:10.1007/978-3-030-56514-5_27
- Authors
- Niu, W., & Qi, Y.
- Affiliations
- Shanghai Jiao Tong University (CN)
- ORCID
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2015-02
- Volume
- 8
- Issue
- 1
- Pages
- 114-121
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- OpenAlex
- W2126922178
- Cited by
- 35
- References
- 66
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 7 · 2017: 6 · 2016: 10 · 2015: 2
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Cardiovascular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- cholesteryl ester transfer protein, coronary artery disease, CETP gene polymorphisms, reverse cholesterol transport, causal relationship, Mendelian randomization
- MeSH terms
- Alleles, Cholesterol, Coronary Artery Disease, Humans, Models, Genetic, Risk Factors, Randomized Controlled Trials as Topic, Cholesterol Ester Transfer Proteins
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