Genetic and other determinants of AMP deaminase activity in healthy adult skeletal muscle

AMPD1 genotype,relative fiber type composition, training status, and gender wereevaluated as contributing factors to the reported variation in AMPdeaminase enzyme activity in healthy skeletal muscle. Multifactorialcorrelative analyses demonstrate thatAMPD1 genotype has the greatest effecton enzyme activity. An AMPD1 mutantallele frequency of 13.7 and a 1.7% incidence of enzyme deficiency wasfound across 175 healthy subjects. Homozygotes for theAMPD1 normal allele have high enzymeactivities, and heterozygotes display intermediate activities. Whenexamined according to genotype, other factors were found to affectvariability as follows: AMP deaminase activity in homozygotes for thenormal allele exhibits a negative correlation with the relativepercentage of type I fibers and training status. Conversely, residualAMP deaminase activity in homozygotes for the mutant allele displays apositive correlation with the relative percentage of type I fibers.Opposing correlations in different homozygousAMPD1 genotypes are likely due torelative fiber-type differences in the expression ofAMPD1 andAMPD3 isoforms. Gender alsocontributes to variation in total skeletal muscle AMP deaminaseactivity, with normal homozygous and heterozygous women showing only85-88% of the levels observed in genotype-matched men.