CONTEXT: Two potassium (K) channel genes, Kcnk3 and Kcnk9, when deleted in mice, produced a model of hyperaldosteronism and hypertension. OBJECTIVE: Our objective was to explore genetic variation [single-nucleotide polymorphisms (SNP)] in KCNK3 and KCNK9 in relation to blood pressure (BP) and aldosterone production in humans. SUBJECTS AND STUDY DESIGN: Two groups of healthy European Americans (EA) and African Americans (AA) were studied: 1) a longitudinal study group (age ∼14 yr when enrolled, 444 EA and 351 AA) and 2) an inpatient cross-sectional study group (age ∼23 yr, 85 EA and 109 AA). Plasma renin activity, plasma aldosterone concentration, and level of serum K were measured cross-sectionally; BP was measured semiannually in the longitudinal study. SNP were selected to provide coverage of the genes for both EA and AA (15 in KCNK3 and 74 in KCNK9). RESULTS: No associations with KCNK3 were observed. In the longitudinal study, multiple SNP in KCNK9 associated with systolic BP in AA, whereas associations were primarily with aldosterone production in EA. The direction of the changes was the same for aldosterone production and BP, whereas serum K changed in the opposite direction. In the cross-sectional study, associations were observed only in AA. Combining the two studies, one SNP in particular, rs888345, was strongly associated with BP in AA and with indices of aldosterone production in AA and EA. CONCLUSION: Results of an exploratory study suggest that BP and aldosterone production may be affected by variations in KCNK9. The findings could have relevance to risk for hypertension.
CONTEXT: Two potassium (K) channel genes, Kcnk3 and Kcnk9, when deleted in mice, produced a model of hyperaldosteronism and hypertension. OBJECTIVE: Our objective was to explore genetic variation [single-nucleotide polymorphisms (SNP)] in KCNK3 and KCNK9 in relation to blood pressure (BP) and aldosterone production in humans. SUBJECTS AND STUDY DESIGN: Two groups of healthy European Americans (EA) and African Americans (AA) were studied: 1) a longitudinal study group (age ∼14 yr when enrolled, 444 EA and 351 AA) and 2) an inpatient cross-sectional study group (age ∼23 yr, 85 EA and 109 AA). Plasma renin activity, plasma aldosterone concentration, and level of serum K were measured cross-sectionally; BP was measured semiannually in the longitudinal study. SNP were selected to provide coverage of the genes for both EA and AA (15 in KCNK3 and 74 in KCNK9). RESULTS: No associations with KCNK3 were observed. In the longitudinal study, multiple SNP in KCNK9 associated with systolic BP in AA, whereas associations were primarily with aldosterone production in EA. The direction of the changes was the same for aldosterone production and BP, whereas serum K changed in the opposite direction. In the cross-sectional study, associations were observed only in AA. Combining the two studies, one SNP in particular, rs888345, was strongly associated with BP in AA and with indices of aldosterone production in AA and EA. CONCLUSION: Results of an exploratory study suggest that BP and aldosterone production may be affected by variations in KCNK9. The findings could have relevance to risk for hypertension.
Authors: David A Calhoun; Daniel Jones; Stephen Textor; David C Goff; Timothy P Murphy; Robert D Toto; Anthony White; William C Cushman; William White; Domenic Sica; Keith Ferdinand; Thomas D Giles; Bonita Falkner; Robert M Carey Journal: Circulation Date: 2008-06-24 Impact factor: 29.690
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Authors: Lucinda A Davies; Changlong Hu; Nick A Guagliardo; Neil Sen; Xiangdong Chen; Edmund M Talley; Robert M Carey; Douglas A Bayliss; Paula Q Barrett Journal: Proc Natl Acad Sci U S A Date: 2008-02-04 Impact factor: 11.205
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Authors: Clive J Hoggart; Giulia Venturini; Massimo Mangino; Felicia Gomez; Giulia Ascari; Jing Hua Zhao; Alexander Teumer; Thomas W Winkler; Natalia Tšernikova; Jian'an Luan; Evelin Mihailov; Georg B Ehret; Weihua Zhang; David Lamparter; Tõnu Esko; Aurelien Macé; Sina Rüeger; Pierre-Yves Bochud; Matteo Barcella; Yves Dauvilliers; Beben Benyamin; David M Evans; Caroline Hayward; Mary F Lopez; Lude Franke; Alessia Russo; Iris M Heid; Erika Salvi; Sailaja Vendantam; Dan E Arking; Eric Boerwinkle; John C Chambers; Giovanni Fiorito; Harald Grallert; Simonetta Guarrera; Georg Homuth; Jennifer E Huffman; David Porteous; Darius Moradpour; Alex Iranzo; Johannes Hebebrand; John P Kemp; Gert J Lammers; Vincent Aubert; Markus H Heim; Nicholas G Martin; Grant W Montgomery; Rosa Peraita-Adrados; Joan Santamaria; Francesco Negro; Carsten O Schmidt; Robert A Scott; Tim D Spector; Konstantin Strauch; Henry Völzke; Nicholas J Wareham; Wei Yuan; Jordana T Bell; Aravinda Chakravarti; Jaspal S Kooner; Annette Peters; Giuseppe Matullo; Henri Wallaschofski; John B Whitfield; Fred Paccaud; Peter Vollenweider; Sven Bergmann; Jacques S Beckmann; Mehdi Tafti; Nicholas D Hastie; Daniele Cusi; Murielle Bochud; Timothy M Frayling; Andres Metspalu; Marjo-Riitta Jarvelin; André Scherag; George Davey Smith; Ingrid B Borecki; Valentin Rousson; Joel N Hirschhorn; Carlo Rivolta; Ruth J F Loos; Zoltán Kutalik Journal: PLoS Genet Date: 2014-07-31 Impact factor: 5.917