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

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R273

First Online: 27 December 2012Received: 16 July 2012Revised: 06 December 2012Accepted: 20 December 2012


IntroductionPotassium 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 multicenter Caucasian SSc cohort.

MethodsThe 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 by using a TaqMan SNP genotyping assay.

ResultsIndividual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets for example, 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 with PAH-negative patients showed no significant differences among patients.

ConclusionsOur data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.

AbbreviationsACAanti-centromere autoantibodies

ATAanti-topoisomerase antibodies

BD testBreslow-Day test

CD226cluster of differentiation 226

CEUUtah residents with ancestry from northern and western Europe

dcSScdiffuse cutaneous systemic sclerosis

hRCTHigh-resolution computed tomography

HWEHardy-Weinberg equilibrium


KCNA5potassium voltage-gated channel shaker-related subfamily member 5

Kv channelspotassium voltage-gated channels

lcSSclimited cutaneous systemic sclerosis

MAFminor allele frequency

NOTCH4 Notch Drosophila homologue 4

ORodds ratio

PAHpulmonary arterial hypertension

PASMCpulmonary artery smooth muscle cell

PCRpolymerase chain reaction

SNPsingle-nucleotide polymorphism

SOX5SRY sex-determining region Y-box 5

SScsystemic sclerosis.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4124 contains supplementary material, which is available to authorized users.

Carmen Fonseca and Javier Martin contributed equally to this work.

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Author: Lara Bossini-Castillo - Carmen P Simeon - Lorenzo Beretta - Jasper Broen - Madelon C Vonk - José Luis Callejas - Patrici

Source: https://link.springer.com/

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