Key result
The prostasin gene rs12597511 CT/TT genotypes were associated with higher diastolic blood pressure than the CC genotype in African-Americans (62.5 vs 60.4 mm Hg, P=0.003) and European-Americans.
Why the study?
Does the rs12597511 polymorphism in the prostasin gene increase blood pressure and pulse wave velocity in healthy youths?
Observational (n=920)
Does the rs12597511 polymorphism in the prostasin gene increase blood pressure and pulse wave velocity in healthy youths?
Absolute Event Rate: 62.5% vs 60.4%
p-value: p=0.003
Genetic variation in the prostasin gene (rs12597511) is associated with higher blood pressure and increased pulse wave velocity in healthy youths, suggesting it as a candidate gene for hypertension.
Supports prostasin rs12597511 as hypertension candidate in youths; leaves open causality and clinical relevance pending prospective studies.
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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Zhu et al. (2008) conducted an observational in Hypertension (n=920). Prostasin gene rs12597511 CT and TT genotypes vs. CC genotype was evaluated on Diastolic blood pressure (DBP) in African-Americans (p=0.003). The prostasin gene rs12597511 CT/TT genotypes were associated with higher diastolic blood pressure than the CC genotype in African-Americans (62.5 vs 60.4 mm Hg, P=0.003) and European-Americans.
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