GENETIC AND OTHER DETERMINANTS OF AMP-DEAMINASE ACTIVITY IN HEALTHY ADULT SKELETAL-MUSCLE

AMPD1 genotype, relative fiber type composition, training status, and gender were evaluated as contributing factors to the reported variatio n in AMP deaminase enzyme activity in healthy skeletal muscle. Multifa ctorial correlative analyses demonstrate that AMPD1 genotype has the g reatest effect on enzyme activity An AMPD1 mutant allele frequency of 13.7 and a 1.7% incidence of enzyme deficiency was found across 175 he althy subjects. Homozygotes for the AMPD1 normal allele have high enzy me activities, and heterozygotes display intermediate activities. When examined according to genotype, other factors were found to affect va riability as follows: AMP deaminase activity in homozygotes for the no rmal allele exhibits a negative correlation with the relative percenta ge of type I fibers and training status. Conversely, residual AMP deam inase activity in homozygotes for the mutant allele displays a positiv e correlation with the relative percentage of type I fibers. Opposing correlations in different homozygous AMPD1 genotypes are likely due to relative fiber-type differences in the expression of AMPD1 and AMPD3 isoforms. Gender also contributes to variation in total skeletal muscl e AMP deaminase activity, with normal homozygous and heterozygous wome n showing only 85-88% of the levels observed in genotype-matched men.