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The KCNMB1 E65K variant is associated with reduced central pulse pressure in the community-based Framingham Offspring Cohort.

Abstract：

OBJECTIVES:Genetic variants that influence large conductance calcium-activated potassium channel's function may alter arterial function and contribute to the known heritability of arterial stiffness and blood pressure. The beta1-subunit (KCNMB1) of the large conductance calcium-activated potassium channel includes two coding region polymorphisms. E65K, a gain-of-function polymorphism, is predicted to enhance large conductance calcium-activated potassium channel opening and vasorelaxation, whereas V110L has no known effect. We and others have reported that E65K carriers have reduced blood pressure. METHODS:To test our hypothesis that E65K has a favorable effect on arterial function, we related arterial tonometry and brachial artery phenotypes to genotypes in 1100 Framingham Offspring Study participants with available genotypes and phenotypes (53% women; mean age 61.5 +/- 9.4 years). RESULTS:The minor allele frequency was 0.10 for E65K and 0.09 for V110L; both were in Hardy-Weinberg equilibrium (chi2, P > 0.05), and haplotype analysis found R2 = 0.01. E65K was associated with lower augmented pressure (7.4 +/- 3.3 versus 9.0 +/- 3.8 mmHg, P = 0.01) and central pulse pressure (47.1 +/- 7.3 versus 50.7 +/- 7.8 mmHg, P = 0.01) in multivariable analyses. No association was noted between E65K and mean arterial pressure, carotid-femoral pulse wave velocity or brachial artery diameter, flow velocity or volume flow. V110L was not associated with tonometry or brachial measures. CONCLUSION:A diminished augmented pressure in K-carriers suggests a reduced or delayed wave reflection and supports the hypothesis that E65K reduces arterial impedance mismatch in the arterial tree. Our findings in a middle-aged community-based cohort, if replicated, would support that E65K has a favorable effect on arterial function and pulsatile hemodynamic load.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Kelley-Hedgepeth A,Peter I,Montefusco MC,Levy D,Benjamin EJ,Vasan RS,Mendelsohn ME,Housman D,Huggins GS,Mitchell GF

doi

10.1097/HJH.0b013e328317c8ae

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

55-60

issue

eissn

0263-6352

issn

1473-5598

pii

00004872-200901000-00012

journal_volume

pub_type

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The KCNMB1 E65K variant is associated with reduced central pulse pressure in the community-based Framingham Offspring Cohort.