title: Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with schistosomes.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France. alain.dessein@univmed.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Dessein
authors.forename: Christophe
authors.initials: C
authors.lastname: Chevillard
authors.forename: Violaine
authors.initials: V
authors.lastname: Arnaud
authors.forename: Xunya
authors.initials: X
authors.lastname: Hou
authors.forename: Anas Ahmed
authors.initials: AA
authors.lastname: Hamdoun
authors.forename: Helia
authors.initials: H
authors.lastname: Dessein
authors.forename: Hongbin
authors.initials: H
authors.lastname: He
authors.forename: Suzan A
authors.initials: SA
authors.lastname: Abdelmaboud
authors.forename: Xinsong
authors.initials: X
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Arthur
authors.initials: A
authors.lastname: Varoquaux
authors.forename: Adil
authors.initials: A
authors.lastname: Mergani
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdelwahed
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Ahmed
authors.initials: A
authors.lastname: Monis
authors.forename: Maira G R
authors.initials: MG
authors.lastname: Pitta
authors.forename: Nagla
authors.initials: N
authors.lastname: Gasmelseed
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cabantous
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Aluizio
authors.initials: A
authors.lastname: Prata
authors.forename: Carlos
authors.initials: C
authors.lastname: Brandt
authors.forename: Nasr Eldin
authors.initials: NE
authors.lastname: Elwali
authors.forename: Laurent
authors.initials: L
authors.lastname: Argiro
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Li
mesh_terms: 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
chemical_list: D009687:Nuclear Proteins; D055513:Connective Tissue Growth Factor