title: Association between a CTGF gene polymorphism and systemic sclerosis in a French population.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by chronic fibrosis of the skin and internal organs. Connective tissue growth factor (CTGF) is believed to be a primary mediator of chronic fibrosis. We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182).
  
  
  METHODS
  We conducted a case-control study with 241 scleroderma patients and 269 controls. Seven SNP were genotyped using the TaqMan system. Univariate and multivariate analyses were performed. In silico electrophoretic mobility shift assay (EMSA), and reverse transcriptase polymerase chain reaction analyses were done to assess the effect of the SNP on CTGF gene expression.
  
  
  RESULTS
  The frequency of the rs9399005TT genotype was significantly lower in SSc patients than in controls. This association remained significant after adjustment for gender. An association was detected between the rs9399005 and the diffuse and limited cutaneous forms. Multivariate analysis between SSc patients and controls taking into account all 7 SNP and sex revealed that only sex and the rs9399005 SNP were associated with disease. DNA analysis by EMSA indicated that the T allele bound nuclear factors that were also bound by the C allele. The binding affinity was higher for the T allele. Analysis of the human database and experiments with human hepatocyte cell line indicated the existence of an alternative transcript containing the rs9399005 polymorphism in its 3'UTR region. In silico analysis indicated that this polymorphism may alter the structure of CTGF messenger RNA.
  
  
  CONCLUSIONS
  These findings suggest that CTGF gene polymorphisms may contribute to susceptibility to scleroderma.
authors.affiliation: INSERM, U906, (Institut Nationale de la Santé et de la Recherche Médicale), Laboratoire d'Immunologie et de Génétique des Maladies Parasitaires, Faculté de Médecine, Université de la Méditerranée (UM) Service de Médecine Interne, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille (AP-HM), UM, Marseille, France. brigitte.granel@univmed.fr
authors.forename: Brigitte
authors.initials: B
authors.lastname: Granel
authors.forename: Laurent
authors.initials: L
authors.lastname: Argiro
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fajardy
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Weiller
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Durand
authors.forename: Yves
authors.initials: Y
authors.lastname: Frances
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dombey
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marquet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lesavre
authors.forename: Patrick
authors.initials: P
authors.lastname: Disdier
authors.forename: Fanny
authors.initials: F
authors.lastname: Bernard
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hatron
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevillard
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000235:genetics*; D012737:Sex Factors
chemical_list: D055513:Connective Tissue Growth Factor