@Article{ecn.2010.0187,
AUTHOR = {Matthew B. B. McCall, Bart Ferwerda, Joost Hopman, Ivo Ploemen, Boubacar Maiga, Modibo Daou, Amagana Dolo, Cornelus C. Hermsen, Ogobara K. Doumbo, George Bedu-Addo, Jos W. van der Meer, Marita Troye-Blomberg, André J. A. M. van der Ven, Ralf R. Schumann, Robert W. Sauerwein, Frank P. Mockenhaupt, Mihai G. Netea},
TITLE = {Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations},
JOURNAL = {European Cytokine Network},
VOLUME = {21},
YEAR = {2010},
NUMBER = {2},
PAGES = {77--83},
URL = {http://www.techscience.com/ECN/v21n2/65864},
ISSN = {1952-4005},
ABSTRACT = {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%. <i>Plasmodium falciparum</i>-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 <i>P. falciparum</i>-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.},
DOI = {10.1684/ecn.2010.0187}
}