IFN-γ Polymorphisms (IFN-γ +2109 and IFN-γ +3810) Are Associated with Severe Hepatic Fibrosis in Human Hepatic Schistosomiasis (Schistosoma mansoni)

Christophe Chevillard, Carole Eboumbou Moukoko, Nasr Eldin M A Elwali, Jay Bream, Bourema Kouriba, Laurent Argiro, Siddig Rahoud, Adil Mergani, Sandrine Henri, Jean Gaudart, Qurashi Mohamed-Ali, Howard A. Young, Alain J. Dessein

Research output: Contribution to journalArticle

Abstract

Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-γ. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-γ gene are associated with PPF. The IFN-γ +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-γ +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-γ mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the α-chain of the IFN-γ receptor, and low IFN-γ producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-γ expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).

Original languageEnglish (US)
Pages (from-to)5596-5601
Number of pages6
JournalJournal of Immunology
Volume171
Issue number10
StatePublished - Nov 15 2003
Externally publishedYes

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Schistosomiasis mansoni
Schistosoma mansoni
Fibrosis
Liver
Extracellular Matrix Proteins
Genes
South America
Nuclear Proteins
Introns
Eggs
Signal Transduction
Public Health
Chromosomes
Cytokines
Inflammation
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Chevillard, C., Moukoko, C. E., Elwali, N. E. M. A., Bream, J., Kouriba, B., Argiro, L., ... Dessein, A. J. (2003). IFN-γ Polymorphisms (IFN-γ +2109 and IFN-γ +3810) Are Associated with Severe Hepatic Fibrosis in Human Hepatic Schistosomiasis (Schistosoma mansoni). Journal of Immunology, 171(10), 5596-5601.

IFN-γ Polymorphisms (IFN-γ +2109 and IFN-γ +3810) Are Associated with Severe Hepatic Fibrosis in Human Hepatic Schistosomiasis (Schistosoma mansoni). / Chevillard, Christophe; Moukoko, Carole Eboumbou; Elwali, Nasr Eldin M A; Bream, Jay; Kouriba, Bourema; Argiro, Laurent; Rahoud, Siddig; Mergani, Adil; Henri, Sandrine; Gaudart, Jean; Mohamed-Ali, Qurashi; Young, Howard A.; Dessein, Alain J.

In: Journal of Immunology, Vol. 171, No. 10, 15.11.2003, p. 5596-5601.

Research output: Contribution to journalArticle

Chevillard, C, Moukoko, CE, Elwali, NEMA, Bream, J, Kouriba, B, Argiro, L, Rahoud, S, Mergani, A, Henri, S, Gaudart, J, Mohamed-Ali, Q, Young, HA & Dessein, AJ 2003, 'IFN-γ Polymorphisms (IFN-γ +2109 and IFN-γ +3810) Are Associated with Severe Hepatic Fibrosis in Human Hepatic Schistosomiasis (Schistosoma mansoni)', Journal of Immunology, vol. 171, no. 10, pp. 5596-5601.
Chevillard, Christophe ; Moukoko, Carole Eboumbou ; Elwali, Nasr Eldin M A ; Bream, Jay ; Kouriba, Bourema ; Argiro, Laurent ; Rahoud, Siddig ; Mergani, Adil ; Henri, Sandrine ; Gaudart, Jean ; Mohamed-Ali, Qurashi ; Young, Howard A. ; Dessein, Alain J. / IFN-γ Polymorphisms (IFN-γ +2109 and IFN-γ +3810) Are Associated with Severe Hepatic Fibrosis in Human Hepatic Schistosomiasis (Schistosoma mansoni). In: Journal of Immunology. 2003 ; Vol. 171, No. 10. pp. 5596-5601.
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abstract = "Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-γ. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-γ gene are associated with PPF. The IFN-γ +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-γ +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-γ mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the α-chain of the IFN-γ receptor, and low IFN-γ producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-γ expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).",
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AU - Chevillard, Christophe

AU - Moukoko, Carole Eboumbou

AU - Elwali, Nasr Eldin M A

AU - Bream, Jay

AU - Kouriba, Bourema

AU - Argiro, Laurent

AU - Rahoud, Siddig

AU - Mergani, Adil

AU - Henri, Sandrine

AU - Gaudart, Jean

AU - Mohamed-Ali, Qurashi

AU - Young, Howard A.

AU - Dessein, Alain J.

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N2 - Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-γ. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-γ gene are associated with PPF. The IFN-γ +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-γ +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-γ mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the α-chain of the IFN-γ receptor, and low IFN-γ producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-γ expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).

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