LINKAGE BETWEEN HEMODYNAMIC PHENOTYPES AND Na, K-ATPase GENES: THE QU??BEC FAMILY STUDY

42 The purpose of this study was to investigate whether genetic variation in the genes encoding the α2 and β1 subunits of the Na,K-ATPase are linked with systolic (SBP) and diastolic (DBP) blood pressure, pulse pressure(PP), rate-pressure product (RPP) and heart rate (HRT) measured at rest (r) and during low-intensity exercise (e). Cross-sectional data were based on 533 subjects who were not using antihypertensive medication from 150 families of Phase two of the Québec Family Study (QFS). Longitudinal data were derived from 338 subjects (from 105 families) who had been measured 12 years earlier in the QFS Phase one. Restriction fragment length polymorphisms (RFLP) at the α2 (exon 1 and exon 21-22 with BglII) and β1 (MspI and PvuII) loci of the Na,K-ATPase were determined. Sib-pair analysis revealed significant linkages between rHRT (p=0.003, number of sib-pairs=283), eHRT(p=0.01, n=237), rRPP (p=0.001, n=283), eRPP (p=0.04, n=226) and rSBP(p=0.045, n=283) and the α2 exon 21-22 marker. Moreover, the changes(Δ) in rPP (p=0.032, n=91) and eHRT (p=0.044) over 12-years were linked with the α2 exon 21-22 marker. Finally, the ΔrSBP (p=0.0007 and 0.024, n=84) and ΔrPP (p=0.016 and 0.019, n=84) were linked with bothβ1 RFLP's. The α2 exon 1 marker showed no linkage with the phenotypes. These data suggest that α2 and β1 genes of the Na,K-ATPase may play a role in the regulation of the hemodynamic phenotypes at rest and during low intensity exercise in healthy subjects.