Angiotensin-converting enzyme ID polymorphism and fitness phenotypes in the HERITAGE family study

It has been suggested that genetic variation in the angiotensin- converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (i)/deletion (d) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (V̇(O₂)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal V̇(O₂) (V̇(O(2max)))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% V̇(O(2max))). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0.0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in V̇(O(2max)), V̇(O₂) at 80% of V̇(O(2max)), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.