CARDIORESPIRATORY RESPONSES TO EXERCISE AND THE C34T AMPD1 GENE POLYMORPHISM IN THE HERITAGE FAMILY STUDY

An inherited form of AMPD deficiency has been attributed to a non-sense mutation (C to T transition in nucleotide 34) in exon 2 of AMPD1 gene. AMPD deficiency causes AMP accumulation, which can lead to the production of adenosine by AMP 5'-nucleotidase. It is known that adenosine accumulation exerts a vasodilatory response, which could have physiological consequences during exercise. PURPOSE To examine associations of the C34T polymorphism of the AMPD1 gene with cardiorespiratory and performance phenotypes during cycling exercise at absolute and relative power outputs progressing to exhaustion before and after endurance training for 20 weeks in the HERITAGE Family Study cohort (n = 779). Since no Blacks were mutant homozygotes (TT), only Caucasians were considered for analysis (400 normal homozygotes, CC; 97 heterozygotes, CT; and 6 TT). RESULTS Sedentary State. Cycling at the absolute workload of 50 W resulted in higher rate of perceived exertion in TT (p < 0.0001). At the relative intensity of 60% of VO2 max, stroke volume was lower in TT (p < 0.05). Maximal values for power output, SBP, HR, VCO2, and RER were lower in TT (p < 0.05). Response to Training. The cardiorespiratory training response at 50 W and at 60% of VO2 max was similar across C34T-AMPD1 genotypes. However, max ventilation, max VO2, and max VCO2 during exercise increased less in TT (p < 0.01). CONCLUSION The results indicate that subjects with the TT genotype at the C34T AMPD1 gene have diminished exercise capacity and cardiovascular and ventilatory responses to exercise. Endurance training improves submaximal exercise cardiorespiratory and performance phenotypes in carriers of the C34T mutation as much as in non-carriers, but the training response of ventilatory phenotypes during maximal exercise is more limited in TT. Supported by multiple grants from NIH