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Human Molecular Genetics, 2003, Vol. 12, No. 4 375-378
© 2003 Oxford University Press

Linkage of mild malaria to the major histocompatibility complex in families living in Burkina Faso

Laurence Flori, Serge Sawadogo, Christelle Esnault, Nicolas Frédéric Delahaye, Francis Fumoux and Pascal Rihet*

Université de la Méditerranée, Marseille, France

Received October 9, 2002; Revised November 27, 2002; Accepted November 29, 2002

Tumor necrosis factor alpha (TNF{alpha}) is thought to be a critical mediator of malaria fever, and mild malaria was previously reported to be linked to the MHC region containing the tumor necrosis factor alpha gene (TNF). Thirty-four families from Burkina Faso were analyzed to test for linkage between polymorphisms within the MHC region and mild malaria using the maximum-likelihood-binomial (MLB) program. Two-point analysis indicated linkage of mild malaria to TNFd (LOD=3.27; P= 5.44x10-5). Using multipoint analysis, we also found evidence for linkage of mild malaria to the MHC region, with a peak close to TNF (LOD=3.86; P=1.22x10-5). Our results support genes within the MHC region being involved in mild malaria. In particular, the genetic variation within TNF may influence susceptibility to mild malaria. Nevertheless, TNF-238, TNF-244 and TNF-308 polymorphisms are unlikely to explain linkage of mild malaria to the MHC region, and the causal mutations remain to be identified.

* To whom correspondence should be addressed at: Université de la Méditerranée, IFR 48, Faculté de Pharmacie, Laboratoire d'immunogénétique et de pharmacologie du paludisme-EA 864, 27 Bd Jean Moulin 13385 Marseille Cedex 5, France. Tel: +33 491803674; Fax: +33 491803674; Email: rihet{at}luminy.univ-mrs.fr


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