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. 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..

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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

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