INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicentre Caucasian SSc cohort.METHODS:2,343 SSc cases (179 PAH positive, confirmed by right heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single nucleotide polymorphism (SNP) was genotyped using a TaqMan SNP genotyping assay.RESULTS:Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (e.g. limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled-analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH positive group. The comparison of PAH positive patients versus PAH negative patients showed no significant differences among patients.CONCLUSIONS:Our data do not support an important role of KCNA5 as a SSc susceptibility factor or as a PAH development genetic marker for SSc patients.

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor.

LUNARDI, Claudio;
2012

Abstract

INTRODUCTION: Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicentre Caucasian SSc cohort.METHODS:2,343 SSc cases (179 PAH positive, confirmed by right heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single nucleotide polymorphism (SNP) was genotyped using a TaqMan SNP genotyping assay.RESULTS:Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (e.g. limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled-analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH positive group. The comparison of PAH positive patients versus PAH negative patients showed no significant differences among patients.CONCLUSIONS:Our data do not support an important role of KCNA5 as a SSc susceptibility factor or as a PAH development genetic marker for SSc patients.
Potassium voltage-gated channel shaker-related subfamily member 5; systemic sclerosis; pulmonary arterial hypertension
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/491155
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