title: KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor.
abstract: BACKGROUND
  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.
authors.forename: Lara
authors.initials: L
authors.lastname: Bossini-Castillo
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Simeon
authors.forename: Lorenzo
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authors.lastname: Beretta
authors.forename: Jasper
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authors.lastname: Broen
authors.forename: Madelon C
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authors.forename: José Luis
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authors.lastname: Callejas
authors.forename: Patricia
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authors.lastname: Carreira
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Rodríguez
authors.forename: Rosa
authors.initials: R
authors.lastname: García-Portales
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Ivan
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authors.lastname: Castellví
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Camps
authors.forename: Carlos
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authors.lastname: Tolosa
authors.forename: Esther
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authors.lastname: Vicente-Rabaneda
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Egurbide
authors.forename: Annemie J
authors.initials: AJ
authors.lastname: Schuerwegh
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authors.initials: R
authors.lastname: Hesselstrand
authors.forename: Claudio
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authors.lastname: Lunardi
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
authors.forename: Paul
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authors.lastname: Shiels
authors.forename: Ariane
authors.initials: A
authors.lastname: Herrick
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Christopher
authors.initials: C
authors.lastname: Denton
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Carmen
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authors.lastname: Fonseca
authors.forename: Javier
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authors.lastname: Martin
mesh_terms: D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D007558:Italy; D051666:Kv1.5 Potassium Channel / Q000235:genetics*; D015810:Linkage Disequilibrium; D009426:Netherlands; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D013030:Spain; D013548:Sweden; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel