RT Journal Article
SR Electronic
T1 Association Between a CTGF Gene Polymorphism and Systemic Sclerosis in a French Population
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.090290
DO 10.3899/jrheum.090290
A1 Brigitte Granel
A1 Laurent Argiro
A1 Eric Hachulla
A1 Isabelle Fajardy
A1 Pierre-Jean Weiller
A1 Jean-Marc Durand
A1 Yves Frances
A1 Anne-Marie Dombey
A1 Sandrine Marquet
A1 Nathalie Lesavre
A1 Patrick Disdier
A1 Fanny Bernard
A1 Pierre-Yves Hatron
A1 Christophe Chevillard
YR 2009
UL http://www.jrheum.org/content/early/2009/12/21/jrheum.090290.abstract
AB 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. Conclusion These findings suggest that CTGF gene polymorphisms may contribute to susceptibility to scleroderma.