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Persistence of full...
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McCall, Matthew B B
(author)
Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations
- Article/chapterEnglish2010
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LIBRIS-ID:oai:DiVA.org:su-45675
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https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-45675URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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.
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Ferwerda, Bart
(author)
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Hopman, Joost
(author)
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Ploemen, Ivo
(author)
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Maiga, Boubacar
(author)
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Daou, Modibo
(author)
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Dolo, Amagana
(author)
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Hermsen, Cornelus C
(author)
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Doumbo, Ogobara K
(author)
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Bedu-Addo, George
(author)
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van der Meer, Jos W
(author)
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Troye-Blomberg, MaritaStockholms universitet,Avdelningen för immunologi(Swepub:su)marita
(author)
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van der Ven, André J A M
(author)
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Schumann, Ralf R
(author)
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Sauerwein, Robert W
(author)
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Mockenhaupt, Frank P
(author)
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Netea, Mihai G
(author)
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Stockholms universitetAvdelningen för immunologi
(creator_code:org_t)
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In:European Cytokine Network21:2, s. 77-831148-54931952-4005
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McCall, Matthew ...
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Ferwerda, Bart
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Hopman, Joost
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Ploemen, Ivo
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Maiga, Boubacar
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Daou, Modibo
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Dolo, Amagana
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Bedu-Addo, Georg ...
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van der Meer, Jo ...
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Troye-Blomberg, ...
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van der Ven, And ...
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Schumann, Ralf R
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Sauerwein, Rober ...
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Netea, Mihai G
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Stockholm University