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Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach
BACKGROUND: Recent randomized controlled trials have challenged the concept that increased high density lipoprotein cholesterol (HDL-C) levels are associated with coronary artery disease (CAD) risk reduction. The causal role of HDL-C in the development of atherosclerosis remains unclear. To increase...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258818/ https://www.ncbi.nlm.nih.gov/pubmed/25366166 http://dx.doi.org/10.1186/s12881-014-0118-1 |
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author | Wu, Zhijun Lou, Yuqing Qiu, Xiaochun Liu, Yan Lu, Lin Chen, Qiujing Jin, Wei |
author_facet | Wu, Zhijun Lou, Yuqing Qiu, Xiaochun Liu, Yan Lu, Lin Chen, Qiujing Jin, Wei |
author_sort | Wu, Zhijun |
collection | PubMed |
description | BACKGROUND: Recent randomized controlled trials have challenged the concept that increased high density lipoprotein cholesterol (HDL-C) levels are associated with coronary artery disease (CAD) risk reduction. The causal role of HDL-C in the development of atherosclerosis remains unclear. To increase precision and to minimize residual confounding, we exploited the cholesteryl ester transfer protein (CETP)-TaqIB polymorphism as an instrument based on Mendelian randomization. METHODS: The Mendelian randomization analysis was performed by two steps. First, we conducted a meta-analysis of 47 studies, including 23,928 cases and 27,068 controls, to quantify the relationship between the TaqIB polymorphism and the CAD risk. Next, the association between the TaqIB polymorphism and HDL-C was assessed among 5,929 Caucasians. We further employed Mendelian randomization to evaluate the causal effect of HDL-C on CAD based on the findings from the meta-analysis. RESULTS: The overall comparison of the B2 allele with the B1 allele yielded a significant risk reduction of CAD (P < 0.0001; OR = 0.88; 95% CI: 0.84–0.92) with substantial between-study heterogeneity (I(2) = 55.2%; P(heterogeneity) <0.0001). The result was not materially changed after excluding the Hardy-Weinberg Equilibrium (HWE)-violation studies. Compared with B1B1 homozygotes, Caucasian carriers of the B2 allele had a 0.25 mmol/L increase in HDL-C level (95% CI: 0.20–0.31; P <0.0001; I(2) = 0; P(heterogeneity) =0.87). However, a 1 standard deviation (SD) elevation in HDL-C levels due to the TaqIB polymorphism, was marginal associated with CAD risk (OR =0.79; 95% CI: 0.54–1.03; P =0.08). CONCLUSIONS: Taken together, our results lend support to the concept that increased HDL-C cannot be translated into a reduction in CAD risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-014-0118-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4258818 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42588182014-12-09 Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach Wu, Zhijun Lou, Yuqing Qiu, Xiaochun Liu, Yan Lu, Lin Chen, Qiujing Jin, Wei BMC Med Genet Research Article BACKGROUND: Recent randomized controlled trials have challenged the concept that increased high density lipoprotein cholesterol (HDL-C) levels are associated with coronary artery disease (CAD) risk reduction. The causal role of HDL-C in the development of atherosclerosis remains unclear. To increase precision and to minimize residual confounding, we exploited the cholesteryl ester transfer protein (CETP)-TaqIB polymorphism as an instrument based on Mendelian randomization. METHODS: The Mendelian randomization analysis was performed by two steps. First, we conducted a meta-analysis of 47 studies, including 23,928 cases and 27,068 controls, to quantify the relationship between the TaqIB polymorphism and the CAD risk. Next, the association between the TaqIB polymorphism and HDL-C was assessed among 5,929 Caucasians. We further employed Mendelian randomization to evaluate the causal effect of HDL-C on CAD based on the findings from the meta-analysis. RESULTS: The overall comparison of the B2 allele with the B1 allele yielded a significant risk reduction of CAD (P < 0.0001; OR = 0.88; 95% CI: 0.84–0.92) with substantial between-study heterogeneity (I(2) = 55.2%; P(heterogeneity) <0.0001). The result was not materially changed after excluding the Hardy-Weinberg Equilibrium (HWE)-violation studies. Compared with B1B1 homozygotes, Caucasian carriers of the B2 allele had a 0.25 mmol/L increase in HDL-C level (95% CI: 0.20–0.31; P <0.0001; I(2) = 0; P(heterogeneity) =0.87). However, a 1 standard deviation (SD) elevation in HDL-C levels due to the TaqIB polymorphism, was marginal associated with CAD risk (OR =0.79; 95% CI: 0.54–1.03; P =0.08). CONCLUSIONS: Taken together, our results lend support to the concept that increased HDL-C cannot be translated into a reduction in CAD risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-014-0118-1) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-23 /pmc/articles/PMC4258818/ /pubmed/25366166 http://dx.doi.org/10.1186/s12881-014-0118-1 Text en © Wu et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Wu, Zhijun Lou, Yuqing Qiu, Xiaochun Liu, Yan Lu, Lin Chen, Qiujing Jin, Wei Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title | Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title_full | Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title_fullStr | Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title_full_unstemmed | Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title_short | Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach |
title_sort | association of cholesteryl ester transfer protein (cetp) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a mendelian randomization approach |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258818/ https://www.ncbi.nlm.nih.gov/pubmed/25366166 http://dx.doi.org/10.1186/s12881-014-0118-1 |
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