Variations in the potassium channel genes KCNK3 and KCNK9 in relation to blood pressure and aldosterone production: an exploratory study.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Departments of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Jeesun
J
Jung
Paula Q
PQ
Barrett
George J
GJ
Eckert
Howard J
HJ
Edenberg
Xiaoling
X
Xuei
Wanzhu
W
Tu
J Howard
JH
Pratt
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D001794:Blood Pressure / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011188:Potassium / Q000097:blood; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics*; D012083:Renin / Q000097:blood
C498655:KCNK9 protein, human; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3; D000450:Aldosterone; D012083:Renin; D011188:Potassium