Advanced

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

Bossini-Castillo, Lara; Simeon, Carmen P.; Beretta, Lorenzo; Broen, Jasper; Vonk, Madelon C.; Luis Callejas, Jose; Carreira, Patricia; Rodriguez-Rodriguez, Luis; Garcia-Portales, Rosa and Gonzalez-Gay, Miguel A., et al. (2012) In Arthritis Research and Therapy 14(6).
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.... (More)
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. (Less)
Please use this url to cite or link to this publication:
@article{b3a83636-7263-4a8d-94eb-30c326ebe5dd,
  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.},
  articleno    = {R273},
  author       = {Bossini-Castillo, Lara and Simeon, Carmen P. and Beretta, Lorenzo and Broen, Jasper and Vonk, Madelon C. and Luis Callejas, Jose and Carreira, Patricia and Rodriguez-Rodriguez, Luis and Garcia-Portales, Rosa and Gonzalez-Gay, Miguel A. and Castellvi, Ivan and Teresa Camps, Maria and Tolosa, Carlos and Vicente-Rabaneda, Esther and Victoria Egurbide, Mara and Schuerwegh, Annemie J. and Hesselstrand, Roger and Lunardi, Claudio and van Laar, Jacob M. and Shiels, Paul and Herrick, Ariane and Worthington, Jane and Denton, Christopher and Radstake, Timothy R. D. J. and Fonseca, Carmen and Martin, Javier},
  issn         = {1478-6362},
  language     = {eng},
  number       = {6},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor},
  url          = {http://dx.doi.org/10.1186/ar4124},
  volume       = {14},
  year         = {2012},
}