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J Appl Physiol 88: 346-351, 2000;
8750-7587/00 $5.00
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Vol. 88, Issue 1, 346-351, January 2000

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

Tuomo Rankinen1, Louis Pérusse2, Ingrid Borecki3, Yvon C. Chagnon2, Jacques Gagnon2, Arthur S. Leon4, James S. Skinner5, Jack H. Wilmore6, D. C. Rao3, and Claude Bouchard1

1 Pennington Biomedical Research Center, Human Genomics Laboratory, Baton Rouge, Louisiana 70808-4124; 2 Physical Activity Sciences Laboratory, Laval University, Ste-Foy G1K 7P4, Québec, Canada; 3 Division of Biostatistics and Departments of Genetics and Psychiatry, Washington University Medical School, St. Louis, Missouri 63110-1093; 4 School of Kinesiology and Leisure Studies, University of Minnesota, Minneapolis, Minnesota 55455; 5 Department of Kinesiology, Indiana University, Bloomington, Indiana 11001; and 6 Department of Health and Kinesiology, Texas A&M University, College Station, Texas 77843-4243

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 (VO2 max) and maximal power output (Wmax) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. VO2 max and Wmax 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 VO2 max (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 Wmax. In the whole cohort, Delta VO2 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, baseline VO2 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 O2/min increase in VO2 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 alpha 2 locus influences the trainability of VO2 max in sedentary Caucasian subjects.

exercise training; sodium-potassium pump; family study


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