Heart rate recovery after maximal exercise is associated with acetylcholine receptor M2 (<i>CHRM2</i>) gene polymorphism

The determinants of heart rate (HR) recovery after exercise are not well known, although attenuated HR recovery is associated with an increased risk of cardiovascular mortality. Because acetylcholine receptor subtype M2 (CHRM2) plays a key role in the cardiac chronotropic response, we tested the hypothesis that, in healthy individuals, the CHRM2 gene polymorphisms might be associated with HR recovery 1 min after the termination of a maximal exercise test, both before and after endurance training. The study population consisted of sedentary men and women (n = 95, 42 +/- 5 yr) assigned to a training (n = 80) or control group (n = 15). The study subjects underwent a 2-wk laboratory-controlled endurance training program, which included five 40-min sessions/wk at 70-80% of maximal HR. HR recovery differed between the intron 5 rs324640 genotypes at baseline (C/C, -33 +/- 10; C/T, -33 +/- 7; and T/T, -40 +/- 11 beats/min, P = 0.008). Endurance training further strengthened the association: the less common C/C homozygotes showed 6 and 12 beats/min lower HR recovery than the C/T heterozygotes or the T/T homozygotes (P = 0.001), respectively. A similar association was found between A/T transversion at the 3'-untranslated region of the CHRM2 gene and HR recovery at baseline (P = 0.025) and after endurance training (P = 0.005). These data suggest that DNA sequence variation at the CHRM2 locus is a potential modifier of HR recovery in the sedentary state and after short-term endurance training in healthy individuals.