Open Access Open Badges Research article

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

Lara Bossini-Castillo1*, Carmen P Simeon2, Lorenzo Beretta3, Jasper Broen45, Madelon C Vonk6, José Luis Callejas7, Patricia Carreira8, Luis Rodríguez-Rodríguez9, Rosa García-Portales10, Miguel A González-Gay11, Ivan Castellví12, María Teresa Camps13, Carlos Tolosa14, Esther Vicente-Rabaneda15, María Victoria Egurbide16, the Spanish Scleroderma Group, Annemie J Schuerwegh17, Roger Hesselstrand18, Claudio Lunardi19, Jacob M van Laar20, Paul Shiels21, Ariane Herrick22, Jane Worthington22, Christopher Denton23, Timothy RDJ Radstake45, Carmen Fonseca23 and Javier Martin1

Author affiliations

1 Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Avenida del Conocimiento s/n, Granada, 18100, Spain

2 Servicio de Medicina Interna, Hospital Valle de Hebron, Passeig de la Vall d'Hebron, 119-129, Barcelona, 08035, Spain

3 Referral Center for Systemic Autoimmune Diseases Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, via Francesco Sforza 28, Milan, 20122, Italy

4 Department of Rheumatology & Clinical Immunology, University Medical Center, Heidelberglaan 100, 3485 CX Utrecht, The Netherlands

5 Laboratory of Translational Immunology, University Medical Center, Heidelberglaan 100, 3485 CX Utrecht, The Netherlands

6 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Geert Grooteplein-Zuid 10, Nijmegen, 6525 GA, The Netherlands

7 Servicio de Medicina Interna, Hospital Clínico Universitario, Avenida Doctor Olóriz 16, Granada, 18012, Spain

8 Servicio de Reumatología, Hospital Universitario 12 de Octubre, Avenida de Córdoba, s/n, Madrid, 28041, Spain

9 Servicio de Reumatología, Hospital Clínico San Carlos, C/Profesor Martín Lagos s/n, Madrid, 28040, Spain

10 Servicio de Reumatología, Hospital Universitario Virgen de la Victoria, Campus Universitario Teatinos s/n, Málaga, 29010, Spain

11 Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, IFIMAV, Avenida Valdecilla 25, Santander, 39008, Spain

12 Servicio de Reumatología, Hospital de la Santa Creu i Sant Pau, C/Sant Antoni Maria Claret 167, Barcelona, 08025, Spain

13 Servicio de Medicina Interna, Hospital Carlos Haya, Avenida Carlos Haya s/n, Málaga, 29010, Spain

14 Servicio de Medicina Interna, Hospital Parc Tauli, Parc del Taulí 1, Sabadell, 08208, Spain

15 Servicio de Reumatología, Hospital Universitario de la Princesa, C Diego de León 62, Madrid, 28006, Spain

16 Servicio de Medicina Interna, Hospital de Cruces, Plaza de Cruces 2, Barakaldo, 48903, Spain

17 Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands

18 Department of Rheumatology, Lund University, Paradisgatan 2, Lund, SE-221 00, Sweden

19 Department of Medicine, Università degli Studi di Verona, Via dell'Artigliere 19, Verona, 37129, Italy

20 Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, Newcastle, NE2 4HH, UK

21 Centre for Rheumatic Diseases, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK

22 Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Stopford Building, Oxford Road, Manchester, M13 9PT, UK

23 Centre for Rheumatology, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 PF, UK

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Citation and License

Arthritis Research & Therapy 2012, 14:R273  doi:10.1186/ar4124

Published: 27 December 2012



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.