Published online
doi:10.1084/jem.20090383
The Journal of Experimental Medicine, Vol. 206, No. 11, 2321-2328
The Rockefeller University Press, 0022-1007 $30.00
© Dessein et al.
Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes
Alain Dessein1,2,3,
Christophe Chevillard1,2,
Violaine Arnaud1,2,
Xunya Hou4,
Anas Ahmed Hamdoun5,
Helia Dessein1,2,
Hongbin He4,
Suzan A. Abdelmaboud5,
Xinsong Luo4,
Jun Li4,
Arthur Varoquaux1,2,
Adil Mergani5,
Mohammed Abdelwahed5,
Jie Zhou4,
Ahmed Monis5,
Maira G.R. Pitta1,2,
Nagla Gasmelseed5,
Sandrine Cabantous1,2,
Yaqing Zhao4,
Aluizio Prata6,
Carlos Brandt7,
Nasr Eldin Elwali5,
Laurent Argiro1,2, and
Yuesheng Li4,8
1 Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France
2 Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France
3 Assistance Publique, Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Laboratoire de Parasitologie-Mycologie, 13005 Marseille, France
4 Hunan Institute of Parasitic Diseases, Yueyang, Hunan 414000, China
5 Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan
6 Faculdade de Medicina do Triangulo Mineiro, Uberaba, 38025-180 Minas Gerais, Brazil
7 Universidade Federal de Pernambuco, Recife, 50670-901 Pernambuco, Brazil
8 Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia
CORRESPONDENCE Alain Dessein: alain.dessein{at}univmed.fr
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 x 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 x 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.
Abbreviations used: CI, confidence interval of OR; CTGF, connective tissue growth factor; ECMP, extracellular matrix protein; HBV, hepatitis B virus; HF, hepatic fibrosis; OR, odds ratio; SNP, single nucleotide polymorphism.
© 2009 Dessein et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
Related Article
-
Pro-fibrotic SNPs
- Amy Maxmen
J. Exp. Med. 2009 206: 2305.
[Full Text]
[PDF]
