OBJECTIVE: The large conductance Ca2+ -dependent potassium channel plays a critical role in the control of vascular tone, coupling local increases in intracellular Ca2+ to membrane hyperpolarization and vascular relaxation. It also impacts blood pressure by modulating the renin-angiotensin-aldosterone system. Previous studies have shown that a polymorphism in the beta1 regulatory subunit of the Ca2+ -dependent potassium channel modulates the risk of diastolic hypertension in humans. METHODS: We have studied polymorphisms in the pore-forming alpha subunit gene (KCNMA1) and their association to hypertension and myocardial infarction. RESULTS: Sequencing of the KCNMA1 gene revealed two genetic variants (polymorphisms C864T and IVS17) in population-based epidemiological studies (4786 participants). We detected a significant increase in the frequency of the IVS17+37T>C polymorphism with severe systolic hypertension (48.3% for normotensive vs. 69% for severe systolic hypertension, P=0.03) and with severe general hypertension (48.7 vs. 65.8%, P=0.04), although the adjusted odd ratios did not reach statistical significance. Four C864T/IVS17 haplotypes were identified. Haplotype 4 (encompassing the C allele of the IVS17 polymorphism and the T allele of the C864T polymorphism) was related with increased severity of systolic and general hypertension as well as increased risk of myocardial infarction. CONCLUSION: Our study provides genetic evidence that highlights the relevance of the Ca2+ -dependent potassium channel in the control of human blood pressure and its impact on cardiovascular disease.
OBJECTIVE: The large conductance Ca2+ -dependent potassium channel plays a critical role in the control of vascular tone, coupling local increases in intracellular Ca2+ to membrane hyperpolarization and vascular relaxation. It also impacts blood pressure by modulating the renin-angiotensin-aldosterone system. Previous studies have shown that a polymorphism in the beta1 regulatory subunit of the Ca2+ -dependent potassium channel modulates the risk of diastolic hypertension in humans. METHODS: We have studied polymorphisms in the pore-forming alpha subunit gene (KCNMA1) and their association to hypertension and myocardial infarction. RESULTS: Sequencing of the KCNMA1 gene revealed two genetic variants (polymorphisms C864T and IVS17) in population-based epidemiological studies (4786 participants). We detected a significant increase in the frequency of the IVS17+37T>C polymorphism with severe systolic hypertension (48.3% for normotensive vs. 69% for severe systolic hypertension, P=0.03) and with severe general hypertension (48.7 vs. 65.8%, P=0.04), although the adjusted odd ratios did not reach statistical significance. Four C864T/IVS17 haplotypes were identified. Haplotype 4 (encompassing the C allele of the IVS17 polymorphism and the T allele of the C864T polymorphism) was related with increased severity of systolic and general hypertension as well as increased risk of myocardial infarction. CONCLUSION: Our study provides genetic evidence that highlights the relevance of the Ca2+ -dependent potassium channel in the control of human blood pressure and its impact on cardiovascular disease.
Authors: Lisheng Ge; Neil T Hoa; Zechariah Wilson; Gabriel Arismendi-Morillo; Xiao-Tang Kong; Rajeev B Tajhya; Christine Beeton; Martin R Jadus Journal: Int Immunopharmacol Date: 2014-07-12 Impact factor: 4.932
Authors: Masayo Koide; Matthew A Nystoriak; Gayathri Krishnamoorthy; Kevin P O'Connor; Adrian D Bonev; Mark T Nelson; George C Wellman Journal: J Cereb Blood Flow Metab Date: 2010-08-25 Impact factor: 6.200
Authors: Alanna C Morrison; Janine F Felix; L Adrienne Cupples; Nicole L Glazer; Laura R Loehr; Abbas Dehghan; Serkalem Demissie; Joshua C Bis; Wayne D Rosamond; Yurii S Aulchenko; Ying A Wang; Talin Haritunians; Aaron R Folsom; Fernando Rivadeneira; Emelia J Benjamin; Thomas Lumley; David Couper; Bruno H Stricker; Christopher J O'Donnell; Kenneth M Rice; Patricia P Chang; Albert Hofman; Daniel Levy; Jerome I Rotter; Ervin R Fox; Andre G Uitterlinden; Thomas J Wang; Bruce M Psaty; James T Willerson; Cornelia M van Duijn; Eric Boerwinkle; Jacqueline C M Witteman; Ramachandran S Vasan; Nicholas L Smith Journal: Circ Cardiovasc Genet Date: 2010-04-17