@article{10902/31405,
year = {2012},
url = {https://hdl.handle.net/10902/31405},
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 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.},
organization = {This work was supported by the following grants: JM was funded by GENFER
from the Spanish Society of Rheumatology, SAF2009-11110 from the
Spanish Ministry of Science, CTS-4977 from Junta de Andalucía, Spain, in part
by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/
0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain, and by Fondo
Europeo de Desarrollo Regional (FEDER). TRDJR was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis
Foundation (National Reumafonds). JM and TRDJR were sponsored by the
Orphan Disease Program grant from the European League Against
Rheumatism (EULAR). BPCK is supported by the Dutch Diabetes Research
Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation
(Reumafonds, grant NR 09-1-408). This study was also funded by PI-0590-
2010, Consejería de Salud, Junta de Andalucía, Spain.},
publisher = {BioMed Central},
publisher = {Arthritis Research & Therapy, 2012, 14(6), R273},
title = {KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor},
author = {Bossini-Castillo, Lara and Simeón, Carmen P. and Beretta, Lorenzo and Broen, Jasper and Vonk, Madelon C. and Callejas, José Luis and Carreira, Patricia and Rodríguez-Rodríguez, Luis and García-Portales, Rosa and González-Gay Mantecón, Miguel Ángel and Castellví, Iván and Camps, María Teresa and Tolosa, Carlos and Vicente-Rabaneda, Esther and Egurbide, María Victoria and Schuerwegh, Annemie J. and Hesselstrand, Roger and Lunardi, Claudio and Laar, Jacob M. van and Shiels, Paul},
}