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

Lookup NU author(s): Professor Jaap Van Laar



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 multicenter Caucasian SSc cohort. Methods: 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. Results: 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. Conclusions: 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.

Publication metadata

Author(s): Bossini-Castillo L, Simeon CP, Beretta L, Broen J, Vonk MC, Callejas JL, Carreira P, Rodriguez-Rodriguez L, Garcia-Portales R, Gonzalez-Gay MA, Castellvi I, Camps MT, Tolosa C, Vicente-Rabaneda E, Egurbide MV, Schuerwegh AJ, Hesselstrand R, Lunardi C, van Laar JM, Shiels P, Herrick A, Worthington J, Denton C, Radstake TRDJ, Fonseca C, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2012

Volume: 14

Issue: 6

Print publication date: 27/12/2012

Date deposited: 21/03/2013

ISSN (electronic): 1478-6354

Publisher: BioMed Central Ltd.


DOI: 10.1186/ar4124


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Funder referenceFunder name
Dutch Arthritis Foundation (National Reumafonds)
Orphan Disease Program grant from the European League Against Rheumatism (EULAR)
Redes Tematicas de Investigacion Cooperativa Sanitaria Program
Fondo Europeo de Desarrollo Regional (FEDER)
GEN-FER from the Spanish Society of Rheumatology
VIDI laureate from the Dutch Association of Research (NWO)
2008.40.001Dutch Diabetes Research Foundation
CTS-4977Junta de Andalucia, Spain
NR 09-1-408Dutch Arthritis Foundation (Reumafonds)
RD08/0075 (RIER)Instituto de Salud Carlos III (ISCIII), Spain
SAF2009-11110Spanish Ministry of Science
PI-0590-2010Consejeria de Salud, Junta de Andalucia, Spain