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. Conclusion: Genetic variation of the prostasin gene may be implicated in the development of hypertension in youths. © 2008 American Journal of Hypertension, Ltd.
CITATION STYLE
Zhu, H., Guo, D., Li, K., Yan, W., Tan, Y., Wang, X., … Dong, Y. (2008). Prostasin: A possible candidate gene for human hypertension. American Journal of Hypertension, 21(9), 1028–1033. https://doi.org/10.1038/ajh.2008.224
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