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

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.

• Authors: Marta Tomás, Esther Vázquez, José M Fernández-Fernández, Isaac Subirana, Cristina Plata, Magda Heras, Joan Vila, Jaume Marrugat, Miguel A Valverde, Mariano Sentí
• Journal: Journal of hypertension (J Hypertens) Vol. 26 Issue 11 Pg. 2147-53 (Nov 2008) ISSN: 0263-6352 [Print] England
• PMID: 18854754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• KCNMA1 protein, human
• KCNMB1 protein, human
• Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
• Large-Conductance Calcium-Activated Potassium Channel beta Subunits

Topics

• Adult
• Aged
• Female
• Genetic Predisposition to Disease
• Humans
• Hypertension (epidemiology, genetics, metabolism)
• Large-Conductance Calcium-Activated Potassium Channel alpha Subunits (genetics, metabolism)
• Large-Conductance Calcium-Activated Potassium Channel beta Subunits (genetics, metabolism)
• Male
• Middle Aged
• Myocardial Infarction (epidemiology, genetics, metabolism)
• Polymorphism, Single Nucleotide
• Population Surveillance
• Risk Factors
• Spain (epidemiology)