AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE family study

We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3.7 ± 0.6 and 3.2 ± 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP₅₀), whereas, in the TT homozygotes, the decrease was 0.4 ± 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP₅₀). Men with the ACE DD genotype showed a slightly greater decrease in DBP₅₀ (4.4 ± 0.6 mmHg) than the II and ID genotypes (2.8 ± 0.7 and 2.4 ± 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP₅₀; the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.