Association of CETP Gene Polymorphisms and Haplotypes with Acute Heart Rate Response to Exercise

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-C_dominant: B = -8.41, p < 0.001; rs708272-G_dominant: B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-C_dominant: OR = 0.44, p = 0.004; rs708272-G_dominant: 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.