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

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.

Simeon, Carmen P. (author)
Beretta, Lorenzo (author)
Broen, Jasper (author)
Vonk, Madelon C. (author)
Luis Callejas, Jose (author)
Carreira, Patricia (author)
Rodriguez-Rodriguez, Luis (author)
Garcia-Portales, Rosa (author)
Gonzalez-Gay, Miguel A. (author)
Castellvi, Ivan (author)
Teresa Camps, Maria (author)
Tolosa, Carlos (author)
Vicente-Rabaneda, Esther (author)
Victoria Egurbide, Mara (author)
Schuerwegh, Annemie J. (author)
Hesselstrand, RogerLund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)reum-rhe (author)
Lunardi, Claudio (author)
van Laar, Jacob M. (author)
Shiels, Paul (author)
Herrick, Ariane (author)
Worthington, Jane (author)
Denton, Christopher (author)
Radstake, Timothy R. D. J. (author)
Fonseca, Carmen (author)
Martin, Javier (author)
Reumatologi och molekylär skelettbiologiSektion III (creator_code:org_t)

In:Arthritis Research and Therapy: Springer Science and Business Media LLC14:61478-63621478-6354

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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