Linkage of the Na,K-ATPase alpha 2 and beta 1 genes with resting and exercise heart rate and blood pressure: cross-sectional and longitudinal observations from the Quebec Family Study.
OBJECTIVE
To investigate whether genetic variations in the genes encoding the alpha and beta subunits of the Na,K-ATPase are linked with hemodynamic phenotypes.


METHODS
Cross-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.


METHODS
Restriction fragment length polymorphisms were examined at the alpha 2 (exon 1 and exon 21-22 with BglII) and beta 1 (Msp I and Pvu II) 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.


RESULTS
Sib-pair analysis revealed relatively strong linkages (P = 0.0003-0.002) between the resting heart rate and rate-pressure product and the alpha 2 exon 21-22 marker and alpha 2 haplotype. Moreover, the alpha 2 exon 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 alpha 2 haplotype 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 beta 1 Msp I marker and the beta 1 haplotype were linked with the resting rate-pressure product (P = 0.007 and 0.003, respectively), and all beta 1 markers 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 alpha 2 exon 21-22 genotype and the postglucose plasma insulin level with regard to resting systolic blood pressure.


CONCLUSIONS
These data suggest that the alpha 2 and beta 1 genes of Na,K-ATPase contribute to the regulation of hemodynamic phenotypes in healthy subjects.
Rankinen
T
T
Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Quebec, Canada.
Pérusse
L
L
Dériaz
O
O
Thériault
G
G
Chagnon
M
M
Nadeau
A
A
Bouchard
C
C
D001794:Blood Pressure / Q000502:physiology*; D003430:Cross-Sectional Studies; D004247:DNA / Q000032:analysis; D015444:Exercise / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D011792:Quebec; D012146:Rest; D012189:Retrospective Studies; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D014505:Urban Population
D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase