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 α2 locus and the response (Δ) of maximal oxygen consumption (V˙o 2 max ) and maximal power output (W˙ max ) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. V˙o 2 max andW˙ 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 ΔV˙o 2 max ( P= 0.054) and stronger linkages between the α2 exon 21–22 marker ( P = 0.005) and α2 haplotype ( P = 0.003) and ΔW˙ max . In the whole cohort, ΔV˙o 2 max in the 3.3-kb homozygotes of the exon 1 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, baselineV˙o 2 max , 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 O 2 /min increase inV˙o 2 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 O 2 /min, respectively ( P = 0.017). These data suggest that genetic variation at the Na + -K + -ATPase α2 locus influences the trainability ofV˙o 2 max in sedentary Caucasian subjects.