Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

María Teruel,Gerard Espinosa,Esmeralda Delgado-Frías,Jasper Broen,Nicolas Hunzelmann,Claudio Lunardi,Alexander Kreuter,Gabriela Riemekasten,Thomas Krieg,Lorenzo Beretta,Rosa García-Portales,Torsten Witte,Miguel A González‐Gay ,Patrícia Carreira ,Annemie J Schuerwegh ,Jörg H W Distler ,María Teresa Camps ,Bobby P C Koeleman ,Paolo Airò ,Alexandre E Voskuyl ,M Gállego ,Carmen P Simeón ,Madelon C Vonk ,Timothy R D J Radstake ,Javier Martín

doi:10.1186/ar3890

Abstract

IntroductionThe 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).MethodsIn 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.ResultsNo 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.ConclusionsOur results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.

Highlights

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)
Taking into account these considerations, we aimed to investigate the potential association of CD40 and CD40LG genes polymorphism with SSc
No evidence of association between CD40 polymorphisms and susceptibility to SSc was observed in the pooled analysis

Summary

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). Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue characterized by excessive fibrosis of the dermis and vascular damage. Previous studies reported the association of CD40 polymorphisms with susceptibility to a number of autoimmune diseases, such as GD [11], multiple sclerosis [12], RA [13,14], Crohn disease [15], and with visual ischemic manifestations in individuals with biopsy-proven giant cell arteritis [16]. Mutations of CD40LG were observed in patients with the hyper-immunoglobulin M (IgM) syndrome [20], and genetic variations located at the 3UTR of the CD40LG gene were associated with two autoimmune diseases, SLE [21] and RA [22]

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