The Impact of Smoking-Associated Genetic Variants on Post-Exercise Heart Rate

Al Ashkar, Habib and Kharrat Helu, Nihad and Kovács, Nóra and Fiatal, Szilvia and Ádány, Róza and Pikó, Péter (2025) The Impact of Smoking-Associated Genetic Variants on Post-Exercise Heart Rate. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (18). No. 8787. ISSN 1661-6596

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Abstract

Smoking has a well-established impact on cardiovascular health, notably through elevated resting heart rate and impaired autonomic regulation—both key risk factors. While nicotine’s acute effects are well documented, the influence of smoking-related genetic variants on heart rate (HR) responses remains unclear. This study investigated the association between selected smoking-related single nucleotide polymorphisms (SNPs) and HR dynamics following physical exertion. A total of 661 Hungarian adults completed the YMCA 3 min step test, with HR measured at rest, immediately post-exercise, and during recovery at 5 and 10 min. Key indices included post-exercise HR (HRaft), HR change (ΔHR), maximum HR percentage (HRmax%), and heart rate recovery coefficient (HRR). Genetic analysis focused on nine SNPs previously linked to smoking behaviours, with a composite genetic risk score derived from the three most influential variants (rs2235186, rs4142041, and rs578776). Associations were examined using adjusted linear regression. No significant relationship was found between any individual SNP and resting HR. However, rs2235186, rs4142041, and rs578776 were consistently associated with elevated HRaft, increased ΔHR, higher HRmax%, and slower HRR. The genetic risk score showed significant correlations with all post-exercise HR measures, suggesting a cumulative genetic effect. These findings indicate that smoking-related genetic predisposition may influence autonomic cardiovascular responses to physical activity. Although resting HR remains unaffected, specific SNPs are linked to post-exercise HR dynamics and recovery, highlighting the potential value of genetic screening in personalised cardiovascular risk assessment among smokers.

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