Genetics
CETP gene polymorphisms are linked to blunted heart rate response to exercise, first study of its kind reports (Int J Mol Sci 2024)
Original title: Association of CETP Gene Polymorphisms and Haplotypes with Acute Heart Rate Response to Exercise
This study examined the association of five CETP gene single-nucleotide polymorphisms and their haplotypes with acute heart rate response (AHRR) to exercise in 607 people from the Hungarian population, using a 3-minute step test, with adjustment for triglyceride and HDL-cholesterol levels to exclude the direct confounding effect of CETP on lipid profile. Two SNPs, rs1532624 and rs708272, showed significant association with lower delta heart rate (B=-8.41 and B=-8.33, both p<0.001) and reduced risk of adverse AHRR (OR=0.44 and OR=0.43). Two haplotypes also showed significant associations with lower delta heart rate and reduced adverse AHRR risk. The authors report this as the first study to link CETP gene polymorphisms with heart rate response, suggesting the CETP-cardiovascular risk association is partly mediated through heart rate response to exercise, in addition to its lipid effects.
Original abstract
Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624-Cdominant: B = -8.41, p < 0.001; rs708272-Gdominant: B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-Cdominant: OR = 0.44, p = 0.004; rs708272-Gdominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3-CAGCA: B = -6.81, p = 0.003; H9-CGGCG: B = -14.64, p = 0.015) and lower risk of adverse AHRR (H3-CAGCA: OR = 0.58, p = 0.040; H9-CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1-AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.