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Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes

Identifieur interne : 007B38 ( Main/Exploration ); précédent : 007B37; suivant : 007B39

Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes

Auteurs : Alain Dessein ; Christophe Chevillard ; Violaine Arnaud ; Xunya Hou ; Anas Ahmed Hamdoun ; Helia Dessein ; Hongbin He ; Suzan A. Abdelmaboud ; Xinsong Luo ; Jun Li ; Arthur Varoquaux ; Adil Mergani ; Mohammed Abdelwahed ; Jie Zhou ; Ahmed Monis ; Maira G. R. Pitta ; Nagla Gasmelseed ; Sandrine Cabantous ; Yaqing Zhao ; Aluizio Prata ; Carlos Brandt ; Nasr Eldin Elwali ; Laurent Argiro ; Yuesheng Li

Source :

RBID : PMC:2768853

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 × 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.


Url:
DOI: 10.1084/jem.20090383
PubMed: 19822645
PubMed Central: 2768853


Affiliations:


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<institution>Assistance Publique, Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Laboratoire de Parasitologie-Mycologie, 13005 Marseille, France</institution>
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<name sortKey="Hou, Xunya" sort="Hou, Xunya" uniqKey="Hou X" first="Xunya" last="Hou">Xunya Hou</name>
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<name sortKey="Hamdoun, Anas Ahmed" sort="Hamdoun, Anas Ahmed" uniqKey="Hamdoun A" first="Anas Ahmed" last="Hamdoun">Anas Ahmed Hamdoun</name>
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<name sortKey="He, Hongbin" sort="He, Hongbin" uniqKey="He H" first="Hongbin" last="He">Hongbin He</name>
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<name sortKey="Abdelmaboud, Suzan A" sort="Abdelmaboud, Suzan A" uniqKey="Abdelmaboud S" first="Suzan A." last="Abdelmaboud">Suzan A. Abdelmaboud</name>
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<name sortKey="Li, Jun" sort="Li, Jun" uniqKey="Li J" first="Jun" last="Li">Jun Li</name>
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<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
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<name sortKey="Monis, Ahmed" sort="Monis, Ahmed" uniqKey="Monis A" first="Ahmed" last="Monis">Ahmed Monis</name>
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<name sortKey="Cabantous, Sandrine" sort="Cabantous, Sandrine" uniqKey="Cabantous S" first="Sandrine" last="Cabantous">Sandrine Cabantous</name>
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<name sortKey="Zhao, Yaqing" sort="Zhao, Yaqing" uniqKey="Zhao Y" first="Yaqing" last="Zhao">Yaqing Zhao</name>
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<name sortKey="Prata, Aluizio" sort="Prata, Aluizio" uniqKey="Prata A" first="Aluizio" last="Prata">Aluizio Prata</name>
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<name sortKey="Brandt, Carlos" sort="Brandt, Carlos" uniqKey="Brandt C" first="Carlos" last="Brandt">Carlos Brandt</name>
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<name sortKey="Elwali, Nasr Eldin" sort="Elwali, Nasr Eldin" uniqKey="Elwali N" first="Nasr Eldin" last="Elwali">Nasr Eldin Elwali</name>
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<name sortKey="Argiro, Laurent" sort="Argiro, Laurent" uniqKey="Argiro L" first="Laurent" last="Argiro">Laurent Argiro</name>
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<name sortKey="Li, Yuesheng" sort="Li, Yuesheng" uniqKey="Li Y" first="Yuesheng" last="Li">Yuesheng Li</name>
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<institution>Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia</institution>
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<title xml:lang="en" level="a" type="main">Variants of CTGF are associated with hepatic fibrosis in Chinese, Sudanese, and Brazilians infected with Schistosomes</title>
<author>
<name sortKey="Dessein, Alain" sort="Dessein, Alain" uniqKey="Dessein A" first="Alain" last="Dessein">Alain Dessein</name>
<affiliation>
<nlm:aff id="aff1">
<institution>Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">
<institution>Assistance Publique, Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Laboratoire de Parasitologie-Mycologie, 13005 Marseille, France</institution>
</nlm:aff>
</affiliation>
</author>
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<name sortKey="Chevillard, Christophe" sort="Chevillard, Christophe" uniqKey="Chevillard C" first="Christophe" last="Chevillard">Christophe Chevillard</name>
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</nlm:aff>
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<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
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<name sortKey="Arnaud, Violaine" sort="Arnaud, Violaine" uniqKey="Arnaud V" first="Violaine" last="Arnaud">Violaine Arnaud</name>
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<name sortKey="Hou, Xunya" sort="Hou, Xunya" uniqKey="Hou X" first="Xunya" last="Hou">Xunya Hou</name>
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<name sortKey="Hamdoun, Anas Ahmed" sort="Hamdoun, Anas Ahmed" uniqKey="Hamdoun A" first="Anas Ahmed" last="Hamdoun">Anas Ahmed Hamdoun</name>
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<name sortKey="Dessein, Helia" sort="Dessein, Helia" uniqKey="Dessein H" first="Helia" last="Dessein">Helia Dessein</name>
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</nlm:aff>
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<name sortKey="He, Hongbin" sort="He, Hongbin" uniqKey="He H" first="Hongbin" last="He">Hongbin He</name>
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<name sortKey="Abdelmaboud, Suzan A" sort="Abdelmaboud, Suzan A" uniqKey="Abdelmaboud S" first="Suzan A." last="Abdelmaboud">Suzan A. Abdelmaboud</name>
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<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
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<name sortKey="Luo, Xinsong" sort="Luo, Xinsong" uniqKey="Luo X" first="Xinsong" last="Luo">Xinsong Luo</name>
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<nlm:aff id="aff4">
<institution>Hunan Institute of Parasitic Diseases, Yueyang, Hunan 414000, China</institution>
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<name sortKey="Li, Jun" sort="Li, Jun" uniqKey="Li J" first="Jun" last="Li">Jun Li</name>
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</author>
<author>
<name sortKey="Varoquaux, Arthur" sort="Varoquaux, Arthur" uniqKey="Varoquaux A" first="Arthur" last="Varoquaux">Arthur Varoquaux</name>
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</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
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<name sortKey="Mergani, Adil" sort="Mergani, Adil" uniqKey="Mergani A" first="Adil" last="Mergani">Adil Mergani</name>
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<nlm:aff id="aff5">
<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
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<author>
<name sortKey="Abdelwahed, Mohammed" sort="Abdelwahed, Mohammed" uniqKey="Abdelwahed M" first="Mohammed" last="Abdelwahed">Mohammed Abdelwahed</name>
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<nlm:aff id="aff5">
<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
<affiliation>
<nlm:aff id="aff4">
<institution>Hunan Institute of Parasitic Diseases, Yueyang, Hunan 414000, China</institution>
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<name sortKey="Monis, Ahmed" sort="Monis, Ahmed" uniqKey="Monis A" first="Ahmed" last="Monis">Ahmed Monis</name>
<affiliation>
<nlm:aff id="aff5">
<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Pitta, Maira G R" sort="Pitta, Maira G R" uniqKey="Pitta M" first="Maira G. R." last="Pitta">Maira G. R. Pitta</name>
<affiliation>
<nlm:aff id="aff1">
<institution>Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
</affiliation>
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<author>
<name sortKey="Gasmelseed, Nagla" sort="Gasmelseed, Nagla" uniqKey="Gasmelseed N" first="Nagla" last="Gasmelseed">Nagla Gasmelseed</name>
<affiliation>
<nlm:aff id="aff5">
<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cabantous, Sandrine" sort="Cabantous, Sandrine" uniqKey="Cabantous S" first="Sandrine" last="Cabantous">Sandrine Cabantous</name>
<affiliation>
<nlm:aff id="aff1">
<institution>Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
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</author>
<author>
<name sortKey="Zhao, Yaqing" sort="Zhao, Yaqing" uniqKey="Zhao Y" first="Yaqing" last="Zhao">Yaqing Zhao</name>
<affiliation>
<nlm:aff id="aff4">
<institution>Hunan Institute of Parasitic Diseases, Yueyang, Hunan 414000, China</institution>
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</affiliation>
</author>
<author>
<name sortKey="Prata, Aluizio" sort="Prata, Aluizio" uniqKey="Prata A" first="Aluizio" last="Prata">Aluizio Prata</name>
<affiliation>
<nlm:aff id="aff6">
<institution>Faculdade de Medicina do Triangulo Mineiro, Uberaba, 38025-180 Minas Gerais, Brazil</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Brandt, Carlos" sort="Brandt, Carlos" uniqKey="Brandt C" first="Carlos" last="Brandt">Carlos Brandt</name>
<affiliation>
<nlm:aff id="aff7">
<institution>Universidade Federal de Pernambuco, Recife, 50670-901 Pernambuco, Brazil</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Elwali, Nasr Eldin" sort="Elwali, Nasr Eldin" uniqKey="Elwali N" first="Nasr Eldin" last="Elwali">Nasr Eldin Elwali</name>
<affiliation>
<nlm:aff id="aff5">
<institution>Institute of Nuclear Medicine, Wad Medani, Gezira, Sudan</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Argiro, Laurent" sort="Argiro, Laurent" uniqKey="Argiro L" first="Laurent" last="Argiro">Laurent Argiro</name>
<affiliation>
<nlm:aff id="aff1">
<institution>Institut National de la Santé et de la Recherche Médicale, U906, 13385 Marseille, France</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">
<institution>Université de la Méditerranée, Institut Fédératif de Recherche 88, Assistance Publique, Hôpitaux de Marseille, Faculté de Médecine Timone, 13385 Marseille, Cedex 5, France</institution>
</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Yuesheng" sort="Li, Yuesheng" uniqKey="Li Y" first="Yuesheng" last="Li">Yuesheng Li</name>
<affiliation>
<nlm:aff id="aff4">
<institution>Hunan Institute of Parasitic Diseases, Yueyang, Hunan 414000, China</institution>
</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff8">
<institution>Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Queensland 4029, Australia</institution>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">The Journal of Experimental Medicine</title>
<idno type="ISSN">0022-1007</idno>
<idno type="eISSN">1540-9538</idno>
<imprint>
<date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>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 [
<italic>CTGF</italic>
]) is located in that region that encodes a strongly fibrogenic molecule. We show that the single nucleotide polymorphism (SNP) rs9402373 that lies close to
<italic>CTGF</italic>
is associated with severe HF (P = 2 × 10
<sup>−6</sup>
; 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
<italic>Schistosoma japonicum</italic>
or
<italic>S. mansoni</italic>
. Furthermore, SNP rs12526196, also located close to
<italic>CTGF</italic>
, is independently associated with severe fibrosis (P = 6 × 10
<sup>−4</sup>
; 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.</p>
</div>
</front>
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<name sortKey="Li, D" uniqKey="Li D">D. Li</name>
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<author>
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<author>
<name sortKey="Zhou, H" uniqKey="Zhou H">H. Zhou</name>
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<name sortKey="Jin, Y" uniqKey="Jin Y">Y. Jin</name>
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<author>
<name sortKey="Maniatis, T" uniqKey="Maniatis T">T. Maniatis</name>
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<name sortKey="Chevillard, Christophe" sort="Chevillard, Christophe" uniqKey="Chevillard C" first="Christophe" last="Chevillard">Christophe Chevillard</name>
<name sortKey="Dessein, Alain" sort="Dessein, Alain" uniqKey="Dessein A" first="Alain" last="Dessein">Alain Dessein</name>
<name sortKey="Dessein, Helia" sort="Dessein, Helia" uniqKey="Dessein H" first="Helia" last="Dessein">Helia Dessein</name>
<name sortKey="Elwali, Nasr Eldin" sort="Elwali, Nasr Eldin" uniqKey="Elwali N" first="Nasr Eldin" last="Elwali">Nasr Eldin Elwali</name>
<name sortKey="Gasmelseed, Nagla" sort="Gasmelseed, Nagla" uniqKey="Gasmelseed N" first="Nagla" last="Gasmelseed">Nagla Gasmelseed</name>
<name sortKey="Hamdoun, Anas Ahmed" sort="Hamdoun, Anas Ahmed" uniqKey="Hamdoun A" first="Anas Ahmed" last="Hamdoun">Anas Ahmed Hamdoun</name>
<name sortKey="He, Hongbin" sort="He, Hongbin" uniqKey="He H" first="Hongbin" last="He">Hongbin He</name>
<name sortKey="Hou, Xunya" sort="Hou, Xunya" uniqKey="Hou X" first="Xunya" last="Hou">Xunya Hou</name>
<name sortKey="Li, Jun" sort="Li, Jun" uniqKey="Li J" first="Jun" last="Li">Jun Li</name>
<name sortKey="Li, Yuesheng" sort="Li, Yuesheng" uniqKey="Li Y" first="Yuesheng" last="Li">Yuesheng Li</name>
<name sortKey="Luo, Xinsong" sort="Luo, Xinsong" uniqKey="Luo X" first="Xinsong" last="Luo">Xinsong Luo</name>
<name sortKey="Mergani, Adil" sort="Mergani, Adil" uniqKey="Mergani A" first="Adil" last="Mergani">Adil Mergani</name>
<name sortKey="Monis, Ahmed" sort="Monis, Ahmed" uniqKey="Monis A" first="Ahmed" last="Monis">Ahmed Monis</name>
<name sortKey="Pitta, Maira G R" sort="Pitta, Maira G R" uniqKey="Pitta M" first="Maira G. R." last="Pitta">Maira G. R. Pitta</name>
<name sortKey="Prata, Aluizio" sort="Prata, Aluizio" uniqKey="Prata A" first="Aluizio" last="Prata">Aluizio Prata</name>
<name sortKey="Varoquaux, Arthur" sort="Varoquaux, Arthur" uniqKey="Varoquaux A" first="Arthur" last="Varoquaux">Arthur Varoquaux</name>
<name sortKey="Zhao, Yaqing" sort="Zhao, Yaqing" uniqKey="Zhao Y" first="Yaqing" last="Zhao">Yaqing Zhao</name>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
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