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Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations

McCall, Matthew B B (author)
Ferwerda, Bart (author)
Hopman, Joost (author)
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Ploemen, Ivo (author)
Maiga, Boubacar (author)
Daou, Modibo (author)
Dolo, Amagana (author)
Hermsen, Cornelus C (author)
Doumbo, Ogobara K (author)
Bedu-Addo, George (author)
van der Meer, Jos W (author)
Troye-Blomberg, Marita (author)
Stockholms universitet,Avdelningen för immunologi
van der Ven, André J A M (author)
Schumann, Ralf R (author)
Sauerwein, Robert W (author)
Mockenhaupt, Frank P (author)
Netea, Mihai G (author)
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 (creator_code:org_t)
2010
2010
English.
In: European Cytokine Network. - 1148-5493 .- 1952-4005. ; 21:2, s. 77-83
Related links:
https://urn.kb.se/re...
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

Keyword

NATURAL SCIENCES
NATURVETENSKAP

Publication and Content Type

ref (subject category)
art (subject category)

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