Referenced in: none

Automatically associated channels: Kv1.5

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

Authors: Lara Bossini-Castillo, Carmen P Simeon, Lorenzo Beretta, Jasper Broen, Madelon C Vonk, José Luis Callejas, Patricia Carreira, Luis Rodríguez-Rodríguez, Rosa García-Portales, Miguel A González-Gay, Ivan Castellví, María Teresa Camps, Carlos Tolosa, Esther Vicente-Rabaneda, María Victoria Egurbide, , Annemie J Schuerwegh, Roger Hesselstrand, Claudio Lunardi, Jacob M van Laar, Paul Shiels, Ariane Herrick, Jane Worthington, Christopher Denton, Timothy R D J Radstake, Carmen Fonseca, Javier Martin

Journal, date & volume: Arthritis Res. Ther., 2012 , 14, R273

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23270786

Abstract
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 multicenter Caucasian SSc cohort.The 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.Individual 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.Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients.