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Lara Bossini-Castillo,
Carmen P Simeon,
Lorenzo Beretta,
Jasper Broen,
Madelon C Vonk,
Jose L Callejas,
Patricia Carreira,
Luis Rodriguez-Rodriguez,
Rosa Garcia-Portales,
Miguel A Gonzalez-Gay, [......],
Roger Hesselstrand,
Claudio Lunardi,
Jacob M van Laar,
Paul Shiels,
Ariane Herrick,
Jane Worthington,
Christopher Denton, Timothy Rdj Radstake,
Carmen Fonseca,
Javier Martin
[show abstract]
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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 multicentre Caucasian SSc cohort. METHODS: 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 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 (e.g. 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 versus PAH negative patients showed no significant differences among patients. CONCLUSIONS: Our data do not support an important role of KCNA5 as a SSc susceptibility factor or as a PAH development genetic marker for SSc patients.
Arthritis research & therapy 12/2012; 14(6):R273. · 4.27 Impact Factor
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María Teruel,
Carmen P Simeon,
Jasper Broen,
Madelon C Vonk,
Patricia Carreira,
Maria Teresa Camps,
Rosa García-Portales,
Esmeralda Delgado-Frías,
Maria Gallego,
Gerard Espinosa, [......],
Thomas Krieg,
Alexander Kreuter,
Jörg Hw Distler,
Nicolas Hunzelmann,
Bobby P Koeleman,
Alexandre E Voskuyl,
Annemie J Schuerwegh,
Miguel Angel González-Gay, Timothy Rdj Radstake,
Javier Martin
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ABSTRACT: INTRODUCTION: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). METHODS: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. RESULTS: No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. CONCLUSIONS: Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.
Arthritis research & therapy 06/2012; 14(3):R154. · 4.27 Impact Factor
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Lara Bossini-Castillo,
Carmen P Simeon,
Lorenzo Beretta,
Jasper C Broen,
Madelon C Vonk,
Raquel Ríos-Fernández,
Gerard Espinosa,
Patricia Carreira,
María T Camps,
Maria J Castillo, [......],
Roger Hesselstrand,
Claudio Lunardi,
Jacob M van Laar,
Meng May Chee,
Ariane Herrick,
Bobby Pc Koeleman,
Christopher P Denton,
Carmen Fonseca, Timothy Rdj Radstake,
Javier Martin
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ABSTRACT: INTRODUCTION: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. METHODS: A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. RESULTS: Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). CONCLUSION: Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.
Arthritis research & therapy 04/2012; 14(2):R85. · 4.27 Impact Factor
