Association of CETP gene polymorphisms and haplotypes with acute heart rate response to exercise

Abstract Background 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 fitness. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Methods Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892 and rs9989419) and their haplotypes (H) known to be associated with cardiovascular risk in the CETP gene with AHRR in 607 individuals from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-minute step test and was measured 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 were applied in the statistical analyses. Results Among the five SNPs examined, two showed a significant association with lower ΔHR (rs1532624-Cdom: B = -8.15, p < 0.001; rs708272-Gdom: B = -8.09, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-A: OR = 2.26, p < 0.001; rs708272-A: OR = 2.17, p < 0.001). Among the ten haplotypes, two showed significant association with lower ΔHR (H3 - CAGCA: B = -6.79, p = 0.003; H9 - CGGCG: B = -14.79, p = 0.014) and lower risk of adverse AHRR (H3 - CAGCA: OR = 0.58, p = 0.038; H9 - CGGCG: OR = 0.05, p = 0.008) compared to the reference haplotype (H1 - AGACG). Conclusions Our study is the first to report a significant association between polymorphisms and their haplotypes in the CETP gene and AHRR. It also confirms that the effect of the CETP gene on cardiovascular risk is expressed through the acute heart rate response to physical activity, in addition to its effect on the lipid profile. Key messages • Certain polymorphisms and haplotypes in the CETP gene show a significant association with AHRR. • The CETP gene polymorphisms exert their effect on cardiovascular risk not only by altering the lipid profile, but also by modifying the heart rate response to physical activity.