Prostasin

A possible candidate gene for human hypertension

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1028-1033
Number of pages6
JournalAmerican journal of hypertension
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2008

Fingerprint

Genotype
Hypertension
Single Nucleotide Polymorphism
Genes
Blood Pressure
Pulse Wave Analysis
HapMap Project
Epithelial Sodium Channels
Nephrons
Serine Proteases
African Americans
prostasin
Phenotype

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Prostasin : A possible candidate gene for human hypertension. / Zhu, Haidong; Guo, Dehuang; Li, Ke; Yan, Weili; Tan, Yuande; Wang, Xiaoling; Treiber, Frank A.; Chao, Julie; Snieder, Harold; Dong, Yanbin.

In: American journal of hypertension, Vol. 21, No. 9, 01.09.2008, p. 1028-1033.

Research output: Contribution to journalArticle

Zhu, H, Guo, D, Li, K, Yan, W, Tan, Y, Wang, X, Treiber, FA, Chao, J, Snieder, H & Dong, Y 2008, 'Prostasin: A possible candidate gene for human hypertension', American journal of hypertension, vol. 21, no. 9, pp. 1028-1033. https://doi.org/10.1038/ajh.2008.224
Zhu, Haidong ; Guo, Dehuang ; Li, Ke ; Yan, Weili ; Tan, Yuande ; Wang, Xiaoling ; Treiber, Frank A. ; Chao, Julie ; Snieder, Harold ; Dong, Yanbin. / Prostasin : A possible candidate gene for human hypertension. In: American journal of hypertension. 2008 ; Vol. 21, No. 9. pp. 1028-1033.
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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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AU - Zhu, Haidong

AU - Guo, Dehuang

AU - Li, Ke

AU - Yan, Weili

AU - Tan, Yuande

AU - Wang, Xiaoling

AU - Treiber, Frank A.

AU - Chao, Julie

AU - Snieder, Harold

AU - Dong, Yanbin

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N2 - 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.

AB - 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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