Association Between a CTGF Gene Polymorphism and Systemic Sclerosis in a French Population
Association Between a CTGF Gene Polymorphism and Systemic Sclerosis in a French Population
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DOI：
10.3899/jrheum.090290
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发表时间：
2010-02-01
影响因子：
3.9
通讯作者：
Chevillard, Christophe
中科院分区：
文献类型：
--
作者：
Granel, Brigitte;Argiro, Laurent;Chevillard, Christophe
Objective.系统性硬化症（SSc）是一种危及生命的自身免疫性疾病，其特征是皮肤和内脏的慢性纤维化。结缔组织生长因子（CTGF）被认为是慢性纤维化的主要介质。我们评估了CTGF基因7个单核苷酸多态性（SNP）与法国人群硬皮病之间的可能关联（登记号2006/0182）。我们对241名硬皮病患者和269名对照进行了病例对照研究。采用TaqMan系统对7个SNP进行基因分型。进行单变量和多变量分析。采用电子迁移率变动分析（EMSA）和逆转录聚合酶链反应（RT-PCR）技术分析SNP对CTGF基因表达的影响。SSc患者rs 9399005 TT基因型频率显著低于对照组。这种关联在调整性别后仍然显着。检测到rs 9399005与弥漫性和有限皮肤形式之间存在关联。SSc患者和对照组之间的多变量分析，考虑到所有7个SNP和性别，显示只有性别和rs 9399005 SNP与疾病相关。EMSA的DNA分析表明，T等位基因结合的核因子也被C等位基因结合。T等位基因的结合亲和力较高。对人类数据库的分析和对人类肝细胞系的实验表明，在其3 'UTR区域存在含有rs 9399005多态性的所有替代转录物。计算机模拟分析表明，该多态性可能改变CTGF信使RNA的结构。提示CTGF基因多态性可能与硬皮病易感性有关。（2009年12月23日首次发布：J Rheumol 2010：37：351-8 doi：10.3899/jrheum.090290）
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 clone to assess the effect of the SNP oil 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 all 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. (First Release Dec 23 2009: J Rheumatol 2010:37:351-8 doi: 10.3899/jrheum.090290)