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 N⁺-K⁺-ATPase α2 locus and the response (Δ) of maximal oxygen consumption (V̇O(2max)) and maximal power output (Ẇ(max)) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. V̇O(2max) and Ẇ(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 α2 (exons 1 and 21-22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the α2 haplotype and ΔV̇O(2max) (P = 0.054) and stronger linkages between the α2 exon 21-22 marker (P = 0.005) and α2 haplotype (P = 0.003) and ΔẆ(max). In the whole cohort, ΔV̇O(2max) in the 3.3-kb homozygotes of the exon 1 mincer (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 V̇O(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) ml O₂/min increase in V̇O₂(max), 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 ml O₂/min, respectively (P = 0.017). These data suggest that genetic variation at the Na⁺K⁺-ATPase α2 locus influences the trainability of V̇O(2max) in sedentary Caucasian subjects.