Ambulatory blood pressure is associated with polymorphic variation in P2X receptor genes.
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 ( approximately 2.5 mm Hg) difference in night diastolic blood pressure per allele and accounted for approximately 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.
Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, United Kingdom.
Julian
J
Palomino-Doza
Thahira J
TJ
Rahman
Peter J
PJ
Avery
Bongani M
BM
Mayosi
Martin
M
Farrall
Hugh
H
Watkins
Christopher R W
CR
Edwards
Bernard
B
Keavney
D000328:Adult; D001794:Blood Pressure / Q000235:genetics*; D018660:Blood Pressure Monitoring, Ambulatory; D002874:Chromosome Mapping; D002940:Circadian Rhythm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7
C548226:P2RX4 protein, human; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; C110590:purinoceptor P2X6