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Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction: Genomewide Analysis Among 18 245 Initially Healthy Women From the Women’s Genome Health Study
Open accessAbstract
Background— Recent trial data have challenged the hypothesis that cholesteryl ester transfer protein (CETP) and high-density lipoprotein cholesterol (HDL-C) have causal roles in atherothrombosis. One method to evaluate this issue is to examine whether polymorphisms in the CETP gene that impact on HDL-C levels also impact on the future development of myocardial infarction. Methods and Results— In a prospective cohort of 18 245 initially healthy American women, we examined over 350 000 singe-nucleotide polymorphisms (SNPs) first to identify loci associated with HDL-C and then to evaluate whether significant SNPs within these loci also impact on rates of incident myocardial infarction during an average 10-year follow-up period. Nine loci on 9 chromosomes had 1 or more SNPs associated with HDL-C at genome-wide statistical significance ( P <5�10 −8 ). However, only SNPs near or in the CETP gene at 16q13 were associated with both HDL-C and risk of incident myocardial infarction (198 events). For example, SNP rs708272 in the CETP gene was associated with a per-allele increase in HDL-C levels of 3.1 mg/dL and a concordant 24% lower risk of future myocardial infarction (age-adjusted hazard ratio, 0.76; 95% CI, 0.62 to 0.94), consistent with recent meta-analysis. Independent and again concordant effects on HDL-C and incident myocardial infarction were also observed at the CETP locus for rs4329913 and rs7202364. Adjustment for HDL-C attenuated but did not eliminate these effects. Conclusion— In this prospective cohort of initially healthy women, SNPs at the CETP locus impact on future risk of myocardial infarction, supporting a causal role for CETP in atherothrombosis, possibly through an HDL-C mediated pathway.
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The Structure of Haplotype Blocks in the Human Genome
Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., et al. (2002) · Science · doi:10.1126/science.1069424 · Cited by 5,863
Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181
Effects of torcetrapib in patients at high risk for coronary events
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J. P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa0706628 · Cited by 3,139
A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women
Ridker, P. M., Cook, N. R., Lee, I.-M., Gordon, D., Gaziano, J. M., Manson, J. E., Hennekens, C. H., & Buring, J. E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050613 · Cited by 1,945
Self-citationNewly identified loci that influence lipid concentrations and risk of coronary artery disease
Willer, C. J., Sanna, S., Jackson, A. U., Scuteri, A., Bonnycastle, L. L., Clarke, R., Heath, S. C., Timpson, N. J., Najjar, S. S., Stringham, H. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.76 · Cited by 1,585
Mendelian randomization: prospects, potentials, and limitations
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Polymorphisms Associated with Cholesterol and Risk of Cardiovascular Events
Kathiresan, S., Melander, O., Anevski, D., Guiducci, C., Burtt, N. P., Roos, C., Hirschhorn, J. N., Berglund, G., Hedblad, B., Groop, L., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706728 · Cited by 696
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Schwartz, G. G., Olsson, A. G., Abt, M., Ballantyne, C. M., Barter, P. J., Brumm, J., Chaitman, B. R., Holme, I. M., Kallend, D., Leiter, L. A., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1206797 · Cited by 2,022
MAGIC, Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., et al. (2010) · Nature Genetics · doi:10.1038/ng.685 · Cited by 931
Self-citationManning, A. K., Hivert, M.-F., Scott, R. A., Grimsby, J. L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.-T., Bielak, L. F., Prokopenko, I., et al. (2012) · Nature Genetics · doi:10.1038/ng.2274 · Cited by 827
Evacetrapib and cardiovascular outcomes in high-risk vascular disease
Lincoff, A. M., Nicholls, S. J., Riesmeyer, J. S., Barter, P. J., Brewer, H. B., Fox, K. A. A., Gibson, C. M., Granger, C., Menon, V., Montalescot, G., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1609581 · Cited by 801
Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.
Swerdlow, D. I., Kuchenbaecker, K. B., Shah, S., Sofat, R., Holmes, M. V., White, J., Mindell, J. S., Kivimaki, M., Brunner, E. J., Whittaker, J. C., et al. (2016) · International Journal of Epidemiology · doi:10.1093/ije/dyw088 · Cited by 387
Metadata
- Authors
- Ridker, P. M., Paré, G., Parker, A. N., Zee, R. Y. L., Miletich, J. P., & Chasman, D. I.
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2009-02
- Volume
- 2
- Issue
- 1
- Pages
- 26-33
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- OpenAlex
- W2166941513
- Cited by
- 200
- References
- 8
- FWCI
- 10.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction: Genomewide Analysis Among 18 245 Initially Healthy Women From the Women’s Genome Health Study. https://app.cochat.ai/papers/10.1161/circgenetics.108.817304
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- Ridker, P. M., Paré, G., Parker, A. N., Zee, R. Y. L., Miletich, J. P., & Chasman, D. I. (2009). Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction: Genomewide Analysis Among 18 245 Initially Healthy Women From the Women’s Genome Health Study. Circulation: Cardiovascular Genetics. https://doi.org/10.1161/circgenetics.108.817304
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