The Na+-K+-ATPase alpha 2 gene and trainability of cardiorespiratory endurance: the HERITAGE Family Study

The Na+-K+-ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance perform ance. This study aimed to investigate the associations between genetic vari ants at the Na+-K+-ATPase alpha 2 locus and the response (Delta) of maximal oxygen consumption ((V)over dot O-2max) and maximal power output ((W)over dot (max)) to 20 wk of endurance training in 472 sedentary Caucasian subjec ts from 99 families. (V)over dot O-2max and (W)over dot (max) were measured during two maximal cycle ergometer exercise tests before and again after t he training program, and restriction fragment length polymorphisms at the N a+-K+-ATPase alpha 2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibli ng-pair linkage analysis revealed marginal evidence for linkage between the alpha 2 haplotype and Delta(V)over dot O-2max (P = 0.054) and stronger lin kages between the alpha 2 exon 21-22 marker (P = 0.005) and alpha 2 haploty pe (P = 0.003) and Delta(W) (max). In the whole cohort, Delta(V)over dot O- 2max in the 3.3-kb homozygotes of the exon I marker (n = 5) was 41% lower t han in the 8.0/3.3-kb heterozygotes (n = 87) and 48% lower than in the 8.0- kb homozygotes (n = 380; P = 0.018, adjusted for age, gender, baseline (V)o ver dot O-2max, and body weight). Among offspring, 10.5/10.5-kb homozygotes (n = 14) of the exon 21-22 marker showed a 571 +/- 56 (SE) mi O-2/min incr ease in (V)over dot O-2max whereas the increases in the 10.5/4.3-kb (n = 93 ) and 4.3/4.3-kb (n = 187) genotypes were 442 +/- 22 and 410 +/- 15 mi O-2/ min, respectively (P = 0.017). These data suggest that genetic variation at the Na+-K+-ATPase alpha 2 locus influences the trainability of (V)over dot O-2max in sedentary Caucasian subjects.