ObjectiveTo investigate whether genetic variations in the genes encoding the α and β subunits of the Na,K-ATPase are linked with hemodynamic phenotypes.Design and participantsCross-sectional data based on 533 subjects (no antihypertensive medication) were obtained from 150 families of phase 2 of the Quebec Family Study, together with longitudinal data from 338 subjects (105 families) who had been measured 12 years earlier in phase 1 of the Quebec Family Study.Main outcome measuresRestriction fragment length polymorphisms were examined at the α2(exon 1 and exon 21–22 withBglII) and β1(MspI andPvuII) loci of Na,K-ATPase. Hemodynamic phenotypes measured included systolic and diastolic blood pressure, heart rate and rate–pressure product at rest and during low-intensity exercise.ResultsSib-pair analysis revealed relatively strong linkages (P= 0.0003–0.002) between the resting heart rate and rate–pressure product and the α2exon 21–22 marker and α2haplotype. Moreover, the α2exon 21–22 marker showed suggestive linkages (P= 0.01 to 0.043) with resting systolic blood pressure and exercise diastolic blood pressure, heart rate and rate–pressure product, and the α2haplotype with exercise diastolic blood pressure and rate–pressure product and the 12-year change in resting systolic blood pressure (P= 0.03 to 0.05). Both the β1MspI marker and the β1haplotype were linked with the resting rate–pressure product (P = 0.007 and 0.003, respectively), and all β1markers showed linkage with the change in resting systolic blood pressure (P= 0.00005 to 0.024). In men, there was a significant (P= 0.01) interaction between the α2exon 21–22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure.ConclusionsThese data suggest that the α2and β1genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.