JLE

European Cytokine Network

MENU

Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations Volume 21, numéro 2, June 2010

Auteurs
Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Department of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands, Malaria Research and Training Centre, Faculty of Medicine, University of Bamako, Bamako, Mali, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, Wenner-Grenn Institute of Immunology, Stockholm University, Stockholm, Sweden, Institute of Microbiology and Hygiene, Charité – University Medical Center, Berlin, Germany, Institute of Tropical Medicine and International Health, Charité – University Medical Center, Berlin, Germany

Background. The full-length (L-) variant of caspase-12 is believed to predispose to sepsis. It has been replaced in the genome of most human populations by the (S-) variant, which leads to premature termination of translation. Strikingly, the L-allele is still widely prevalent in African populations, presumably due to a counterbalancing selective force specific to this continent, for which malaria is a prime candidate. Methods. We investigated associations between caspase-12 genotype and malarial parameters in three West-African populations, in studies encompassing immunological, clinical and obstetric data. Results. The caspase-12 L-allele was found at frequencies of 11-34%. Plasmodium falciparum-stimulated mononuclear cells from S/L heterozygote donors produced stronger interferon-γ and interleukin-10 responses than S/S homozygotes (p = 0.011 and p = 0.023 in uninfected and infected donors respectively). Nevertheless, we found no association between caspase-12 genotype and either the presentation of severe malaria or individual clinical parameters in sick children. Amongst pregnant women, the caspase-12 genotype did not influence peripheral or placental malaria infection, or basic obstetric parameters. Interestingly, perinatal mortality was more frequent in children of both S/S and L/L than S/L mothers, independent of placental P. falciparum-infection. Conclusion. We find little clinical or epidemiological evidence that malaria has contributed to the persistence of functional caspase-12 in Africa, suggesting either that alternative selective forces are at work or that genetic drift underlies its current global distribution.