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Infection and Immunity, October 2003, p. 5456-5460, Vol. 71, No. 10
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.10.5456-5460.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

No Evidence for a Major Effect of Tumor Necrosis Factor Alpha Gene Polymorphisms in Periportal Fibrosis Caused by Schistosoma mansoni Infection

Immunologie et Génétique des Maladies Parasitaires, Institut National de la Santé et de la Recherche Médicale, INSERM U399, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Marseille, France,¹ Institute of Nuclear Medicine and Molecular Biology, University of Gezira, Wad Medani,² Al Zaiem Al Azhari University, Omdurman, Sudan³

Received 30 January 2003/ Returned for modification 23 April 2003/ Accepted 13 July 2003

Hepatic periportal fibrosis (PPF), associated with portal hypertension, is a major pathological consequence of infections with Schistosoma mansoni and Schistosoma japonicum. Indeed, affected subjects may die from portal hypertension. Previous studies have indicated that tumor necrosis factor alpha (TNF-) may aggravate fibrosis. We therefore investigated whether PPF was associated with certain polymorphisms of the TNF- gene. Four polymorphisms (TNF- -376 G/A, -308 G/A, -238 G/A, and +488 G/A) were investigated in two Sudanese populations living in an area in which S. mansoni is endemic. These polymorphisms were analyzed for 105 Sudanese subjects with various grades of PPF, from mild to advanced; all subjects were from two neighboring villages (Taweela and Umzukra). They were then analyzed for 70 subjects with advanced liver disease and for 345 matched controls from the Gezira region. We found no evidence of associations between these four polymorphisms and PPF in both of these studies. Thus, these four polymorphisms, two of which (TNF- -376 and -308) were found to increase TNF- gene transcription, are unlikely to have a major effect on PPF progression in these populations. However, this result does not exclude the possibility that these polymorphisms have a minor effect on PPF development.

Editor: W. A. Petri, Jr.

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