Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Sep;21(9):1028-33.
doi: 10.1038/ajh.2008.224. Epub 2008 Jun 26.

Prostasin: a possible candidate gene for human hypertension

Haidong Zhu  1 , Dehuang Guo, Ke Li, Weili Yan, Yuande Tan, Xiaoling Wang, Frank A Treiber, Julie Chao, Harold Snieder, Yanbin Dong
Affiliations

Prostasin: a possible candidate gene for human hypertension

Haidong Zhu et al. Am J Hypertens. 2008 Sep.

Abstract

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..

PubMed Disclaimer

Conflict of interest statement

DISCLOSURES

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Structure of the Prostasin gene. Exons are shown as boxes, introns and intergenic regions as lines
rs2855475 is in the 5’ region close to a GC box, rs12597511 is in the intron 2 region, and rs1549294 and rs1549295 are in the 3’ region.
Figure 2
Figure 2. SBP and DBP in AAs and EAs according to rs12597511
CT +TT genotype carriers compared with CC carriers had higher SBP and DBP in AAs and higher DBP in EAs, after adjustment of age, gender and BMI
See this image and copyright information in PMC

References

    1. Gormley K, Dong Y, Sagnella GA. Regulation of the epithelial sodium channel by accessory proteins. Biochem J. 2003;371:1–14. - PMC - PubMed
    1. Persu A, Barbry P, Bassilana F, Houot AM, Mengual R, Lazdunski M, Corvol P, Jeunemaitre X. Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension. Hypertension. 1998;32:129–137. - PubMed
    1. Baker EH, Dong YB, Sagnella GA, Rothwell M, Onipinla AK, Markandu ND, Cappuccio FP, Cook DG, Persu A, Corvol P, Jeunemaitre X, Carter ND, MacGregor GA. Association of hypertension with T594M mutation in beta subunit of epithelial sodium channels in black people resident in London. Lancet. 1998;351:1388–1392. - PubMed
    1. Persu A, Coscoy S, Houot AM, Corvol P, Barbry P, Jeunemaitre X. Polymorphisms of the gamma subunit of the epithelial Na+ channel in essential hypertension. J Hypertens. 1999;17:639–645. - PubMed
    1. Ambrosius WT, Bloem LJ, Zhou L, Rebhun JF, Snyder PM, Wagner MA, Guo C, Pratt JH. Genetic variants in the epithelial sodium channel in relation to aldosterone and potassium excretion and risk for hypertension. Hypertension. 1999;34:631–637. - PubMed

Publication types