Prostasin: a possible candidate gene for human hypertension.
BACKGROUND
Prostasin, a serine protease, is suggested to be a novel mechanism regulating the epithelial sodium channel (ENaC) expressed in the distal nephron. This study aimed to evaluate whether the human prostasin gene is a novel candidate gene underlying blood pressure (BP) elevation.


METHODS
In a sample of healthy African-American (AA) and European-American (EA) twin subjects aged 17.6 +/- 3.3 years (n = 920, 45% AAs), race-specific tagging single-nucleotide polymorphisms (tSNPs) were identified to tag all the available SNPs +/- 2 kb up- and downstream of the prostasin gene from HapMap at r2 of 0.8-1.0. Selection yielded four tSNPs in AAs and one in EAs, with one tSNP (rs12597511: C to T) present in both AAs and EAs.


RESULTS
For rs12597511, CT and TT genotypes exhibited higher systolic BP (SBP) than CC genotype (115.9 +/- 1.1 mm Hg vs. 113.7 +/- 0.6 mm Hg, P = 0.025 (AAs); and 110.7 +/- 0.5 mm Hg vs. 109.6 +/- 0.6 mm Hg, P = 0.115 (EAs)). CT and TT genotypes compared with CC genotype showed a significant increase in diastolic BP (DBP) in both racial groups (62.5 +/- 0.7 mm Hg vs. 60.4 +/- 0.4 mm Hg, P = 0.003 (AAs); and 58.2 +/- 0.3 mm Hg vs. 56.7 +/- 0.4 mm Hg, P = 0.007 (EAs)). Furthermore, there was an increase in radial pulse wave velocity (PWV) in subjects with CT and TT genotype as compared with those with CC genotype (6.5 +/- 0.1 vs. 6.1 +/- 0.1 m/s, P < 0.0001) (EAs); and 6.7 +/- 0.1 vs. 6.6 +/- 0.1 m/s, P = 0.354 (AAs)). Analyses combining AAs and EAs consistently demonstrated a statistical significance of rs12597511 on all the phenotypes including SBP/DBP and PWV.


CONCLUSIONS
Genetic variation of the prostasin gene may be implicated in the development of hypertension in youths..
Zhu
Haidong
H
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia, USA.
Guo
Dehuang
D
Li
Ke
K
Yan
Weili
W
Tan
Yuande
Y
Wang
Xiaoling
X
Treiber
Frank A
FA
Chao
Julie
J
Snieder
Harold
H
Dong
Yanbin
Y
D000293:Adolescent; D000483:Alleles; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D044469:Racial Groups; D012697:Serine Endopeptidases / Q000235:genetics*; D000099271:Prostasin
D012697:Serine Endopeptidases; D000099271:Prostasin