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J Hypertens. 2008 Nov;26(11):2147-53. doi: 10.1097/HJH.0b013e32831103d8.

Genetic variation in the KCNMA1 potassium channel alpha subunit as risk factor for severe essential hypertension and myocardial infarction.

Author information

1
Unitat de Lípids i Epidemiologia Cardiovascular, Grup d'Epidemiologia i Genètica Cardiovasculars, Program of Research in Inflammatory and Cardiovascular Disorders, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.

Abstract

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.

Comment in

PMID:
18854754
DOI:
10.1097/HJH.0b013e32831103d8
[Indexed for MEDLINE]

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