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Single nucleotide polymorphisms in cholesteryl ester transfer protein gene and recurrent coronary heart disease or mortality in patients with established atherosclerosis.

ABSTRACT: It is not known whether genetic variants in the cholesteryl ester transfer protein (CETP) gene are associated with recurrent coronary heart disease events or mortality in secondary prevention patients. Among 3,717 patients with acute coronary syndrome or coronary artery bypass grafting (CABG) enrolled in a prospective genetic registry, we evaluated whether CETP gene variants previously shown to be associated with reduced CETP activity and high-density lipoprotein cholesterol increase ("A" allele for both TaqIB [rs708272] and rs12149545) are associated with a reduction in recurrent myocardial infarction (MI), recurrent revascularization, or death. At 4.5 years of follow-up, 439 recurrent MI, 698 recurrent revascularizations, and 756 deaths occurred. Using an additive model of inheritance, the "A" allele for rs708272 was not associated with recurrent MI (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78 to 1.17 for AG; HR 0.89, 95% CI 0.67 to 1.19 for AA; compared with GG genotype), recurrent revascularization (HR 1.13, 95% CI 0.95 to 1.33 for AG; HR 1.05, 95% CI 0.84 to 1.32 for AA), or mortality (HR 1.02, 95% CI 0.86 to 1.19 for AG; HR 1.11, 95% CI 0.91 to 1.37 for AA) in the overall cohort. Similar results were seen for the "A" allele for rs12149545. In the CABG subgroup, AG genotype for rs708272 was associated with an increased mortality (HR 1.38, 95% CI 1.06 to 1.79) compared with GG genotype. Results remained consistent using dominant model of inheritance. In conclusion, genetic CETP variants were not associated with recurrent MI or recurrent revascularization in overall cohort with a possible mortality increase in patients who underwent CABG.

SUBMITTER: Virani SS

PROVIDER: S-EPMC3800478 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms in cholesteryl ester transfer protein gene and recurrent coronary heart disease or mortality in patients with established atherosclerosis.

Virani Salim S SS Lee Vei-Vei VV Brautbar Ariel A Grove Megan L ML Nambi Vijay V Alam Mahboob M Elayda MacArthur M Wilson James M JM Willerson James T JT Boerwinkle Eric E Ballantyne Christie M CM

The American journal of cardiology 20130725 9

It is not known whether genetic variants in the cholesteryl ester transfer protein (CETP) gene are associated with recurrent coronary heart disease events or mortality in secondary prevention patients. Among 3,717 patients with acute coronary syndrome or coronary artery bypass grafting (CABG) enrolled in a prospective genetic registry, we evaluated whether CETP gene variants previously shown to be associated with reduced CETP activity and high-density lipoprotein cholesterol increase ("A" allele ...[more]

PMID: 23891427

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Project description:AimsThis meta-analysis aimed to assess the association of the polymorphisms of cholesterol ester transfer protein (CETP) rs708272 (G>A), rs5882 (G>A), rs1800775 (C>A), rs4783961 (G>A), rs247616 (C>T), rs5883 (C>T), rs1800776 (C>A), and rs1532624 (C>A) with coronary artery disease (CAD) and the related underlying mechanisms.MethodsA comprehensive search was performed using five databases such as PubMed, EMBASE, Web of Science, Cochrane Library and Scopus to obtain the appropriate articles. The quality of the included studies was assessed by the Newcastle-Ottawa Scale. The statistical analysis of the data was performed using STATA 17.0 software. The association between CETP gene polymorphisms and risk of CAD was estimated using the pooled odds ratio (OR) and 95% confidence interval (95% CI). The association of CETP gene polymorphisms with lipids and with CETP levels was assessed using the pooled standardized mean difference and corresponding 95% CI. P < 0.05 was considered statistically significant.ResultsA total of 70 case-control studies with 30,619 cases and 31,836 controls from 46 articles were included. The results showed the CETP rs708272 polymorphism was significantly associated with a reduced risk of CAD under the allele model (OR = 0.846, P < 0.001), the dominant model (OR = 0.838, P < 0.001) and the recessive model (OR = 0.758, P < 0.001). AA genotype and GA genotype corresponded to higher high-density lipoprotein cholesterol (HDL-C) concentrations in the blood compared with GG genotype across the studied groups (all P < 0.05). The CETP rs5882 and rs1800775 polymorphisms were not significantly associated with CAD under the allele model (P = 0.802, P = 0.392), the dominant model (P = 0.556, P = 0.183) and the recessive model (P = 0.429, P = 0.551). Similarly, the other mentioned gene polymorphisms were not significantly associated with CAD under the three genetic models.ConclusionsThe CETP rs708272 polymorphism shows a significant association with CAD, and the carriers of the allele A are associated with a lower risk of CAD and higher HDL-C concentrations in the blood compared to the non-carriers. The CETP rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624 are not significantly associated with CAD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.

Dataset Information

Single nucleotide polymorphisms in cholesteryl ester transfer protein gene and recurrent coronary heart disease or mortality in patients with established atherosclerosis.

Publications

Single nucleotide polymorphisms in cholesteryl ester transfer protein gene and recurrent coronary heart disease or mortality in patients with established atherosclerosis.

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