Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes.
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.
Dessein
Alain
A
Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France. alain.dessein@univmed.fr
Chevillard
Christophe
C
Arnaud
Violaine
V
Hou
Xunya
X
Hamdoun
Anas Ahmed
AA
Dessein
Helia
H
He
Hongbin
H
Abdelmaboud
Suzan A
SA
Luo
Xinsong
X
Li
Jun
J
Varoquaux
Arthur
A
Mergani
Adil
A
Abdelwahed
Mohammed
M
Zhou
Jie
J
Monis
Ahmed
A
Pitta
Maira G R
MG
Gasmelseed
Nagla
N
Cabantous
Sandrine
S
Zhao
Yaqing
Y
Prata
Aluizio
A
Brandt
Carlos
C
Elwali
Nasr Eldin
NE
Argiro
Laurent
L
Li
Yuesheng
Y
D000383:Agriculture; D044467:American Indian or Alaska Native / Q000235:genetics; D000818:Animals; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D001938:Brazil; D002460:Cell Line; D002681:China; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005398:Fisheries; D020022:Genetic Predisposition to Disease; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000469:parasitology*; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011485:Protein Binding; D020871:RNA Stability; D012547:Schistosoma / Q000502:physiology; D012552:Schistosomiasis / Q000150:complications* / Q000235:genetics* / Q000469:parasitology; D013397:Sudan; D014158:Transcription, Genetic; D000078329:Workforce
D009687:Nuclear Proteins; D055513:Connective Tissue Growth Factor