Genetics
Meta-analysis of 70 studies confirms CETP rs708272 is linked to lower coronary artery disease risk and higher HDL cholesterol (Front Cardiovasc Med 2023)
Original title: Association of the polymorphisms of the cholesteryl ester transfer protein gene with coronary artery disease: a meta-analysis
This meta-analysis assessed the association of eight CETP gene polymorphisms with coronary artery disease (CAD) risk across 70 case-control studies from 46 articles, comprising 30,619 cases and 31,836 controls. The CETP rs708272 polymorphism was significantly associated with reduced CAD risk under the allele model (OR=0.846, P<0.001), dominant model (OR=0.838, P<0.001), and recessive model (OR=0.758, P<0.001), and its AA and GA genotypes corresponded to higher HDL-cholesterol concentrations than the GG genotype (all P<0.05). The other seven polymorphisms tested, rs5882, rs1800775, rs4783961, rs247616, rs5883, rs1800776, and rs1532624, were not significantly associated with CAD under any genetic model. The authors conclude carriers of the rs708272 A allele have both lower CAD risk and higher HDL-cholesterol than non-carriers.
Original abstract
Aims: This 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.
Methods: A 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.
Results: A 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.
Conclusions: The 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 Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432865, identifier: CRD42023432865.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.