TY - JOUR
T1 - Prostasin
T2 - A possible candidate gene for human hypertension
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
N1 - Funding Information:
Acknowledgments:this study was supported by grants from the National Heart, Lung, and blood Institute (HL77230, HL076723, HL85817, and HL69999) and the American Heart Association (0430078N and 0435146N).
PY - 2008/9
Y1 - 2008/9
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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U2 - 10.1038/ajh.2008.224
DO - 10.1038/ajh.2008.224
M3 - Article
C2 - 18583984
AN - SCOPUS:50249083855
SN - 0895-7061
VL - 21
SP - 1028
EP - 1033
JO - American journal of hypertension
JF - American journal of hypertension
IS - 9
ER -