The Na+-K+-ATPase α2 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 performance. This study aimed to investigate the associations between genetic variants 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 subjects 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 the training program, and restriction fragment length polymorphisms at the Na+-K+-ATPase alpha 2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-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 linkages between the alpha 2 exon 21-22 marker (P = 0.005) and alpha 2 haplotype (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 than 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)over 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 increase 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.