Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes.
Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes.
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DOI：
10.1084/jem.20090383
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发表时间：
2009-10-26
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Dessein A;Chevillard C;Arnaud V;Hou X;Hamdoun AA;Dessein H;He H;Abdelmaboud SA;Luo X;Li J;Varoquaux A;Mergani A;Abdelwahed M;Zhou J;Monis A;Pitta MG;Gasmelseed N;Cabantous S;Zhao Y;Prata A;Brandt C;Elwali NE;Argiro L;Li Y
异常纤维化发生在慢性肝脏炎症期间，并且是丙型肝炎病毒和病毒性肝炎感染中死亡的主要原因。肝纤维化（HF）可能会缓慢或迅速发展，在受试者中的单克隆抗体感染。这在一定程度上取决于染色体6 q23基因的主要遗传控制。一个基因（结缔组织生长因子[CTGF]）位于该区域，编码一种强烈的纤维化分子。我们发现，在两个感染日本血吸虫或血吸虫的中国人、苏丹人和巴西人样本中，与CTGF接近的单核苷酸多态性（SNP）rs 9402373与严重HF相关（P = 2 × 10−6;比值比[OR] = 2.01; OR [CI]的置信区间= 1.51-2.7）。mansoni此外，SNP rs 12526196也位于CTGF附近，在中国和苏丹受试者中与严重纤维化独立相关（P = 6 × 10−4; OR = 1.94; CI = 1.32-2.82）。这两种变体都影响核因子结合，并可能改变基因转录或转录稳定性。所鉴定的变异体可能是预测疾病进展的有价值的标志物，并鉴定HF发展中的关键步骤，其可能是化疗的靶点。
Abnormal fibrosis occurs during chronic hepatic inflammations and is the principal cause of death in hepatitis C virus and schistosome infections. Hepatic fibrosis (HF) may develop either slowly or rapidly in schistosome-infected subjects. This depends, in part, on a major genetic control exerted by genes of chromosome 6q23. A gene (connective tissue growth factor [CTGF]) is located in that region that encodes a strongly fibrogenic molecule. We show that the single nucleotide polymorphism (SNP) rs9402373 that lies close to CTGF is associated with severe HF (P = 2 × 10−6; odds ratio [OR] = 2.01; confidence interval of OR [CI] = 1.51–2.7) in two Chinese samples, in Sudanese, and in Brazilians infected with either Schistosoma japonicum or S. mansoni. Furthermore, SNP rs12526196, also located close to CTGF, is independently associated with severe fibrosis (P = 6 × 10−4; OR = 1.94; CI = 1.32–2.82) in the Chinese and Sudanese subjects. Both variants affect nuclear factor binding and may alter gene transcription or transcript stability. The identified variants may be valuable markers for the prediction of disease progression, and identify a critical step in the development of HF that could be a target for chemotherapy.
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