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(Hypertension. 2008;52:980.)
© 2008 American Heart Association, Inc.

Original Articles

Ambulatory Blood Pressure Is Associated With Polymorphic Variation in P2X Receptor Genes

Julian Palomino-Doza; Thahira J. Rahman; Peter J. Avery; Bongani M. Mayosi; Martin Farrall; Hugh Watkins; Christopher R.W. Edwards; Bernard Keavney

From the Institute of Human Genetics (J.P.-D., T.J.R., B.K.), School of Mathematics and Statistics (P.J.A.), and Office of the Vice Chancellor (C.R.W.E.), Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Medicine (B.M.M.), University of Cape Town, Cape Town, South Africa; and the Department of Cardiovascular Medicine (M.F., H.W.), University of Oxford, Oxford, United Kingdom.

Correspondence to Bernard Keavney, Institute of Human Genetics, Central Parkway, Newcastle upon Tyne, NE1 3BZ United Kingdom. E-mail b.d.keavney{at}ncl.ac.uk

The P2X receptor gene family encodes a series of proteins that function as ATP-gated nonselective ion channels. P2X receptor channels are involved in transducing aldosterone-mediated signaling in the distal renal tubule and are potential candidate genes for blood pressure regulation. We performed a family based quantitative genetic association study in 248 families ascertained through a proband with hypertension to investigate the relationship between common genetic variation in the P2X4, P2X6, and P2X7 genes and ambulatory blood pressure. We genotyped 28 single nucleotide polymorphisms, which together captured the common genetic variability in the 3 genes. We corrected our results for multiple comparisons specifying a false discovery rate of 5%. We found significant evidence of association between the single nucleotide polymorphism rs591874 in the first intron of the P2X7 gene and blood pressure. The strongest association was found for nighttime diastolic blood pressure (P=0.0032), although association was present for both systolic and diastolic blood pressures measured by an observer during the day and at night. Genotypes were associated with a 0.2 SD (2.5 mm Hg) difference in night diastolic blood pressure per allele and accounted for 1% of the total variability in this measurement. Other suggestive associations were found, but these were nonsignificant after correction for multiple testing. These genetic data suggest that drugs affecting P2X receptor signaling may have promise as clinical antihypertensive agents.

Key Words: blood pressure monitoring • ambulatory • hypertension • receptors • purinergic • purinoceptor P2X6 • purinoceptor P2X4 • purinoceptor P2X7