Fc Gamma Receptor IIIB (FcɣRIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Children

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dc.contributor.authorAdu, Bright
dc.contributor.authorDodoo, Daniel
dc.contributor.authorAdukpo, Selorme
dc.contributor.authorHedley, Paula L.
dc.contributor.authorArthur, Fareed K. N.
dc.contributor.authorGerds, Thomas A.
dc.contributor.authorLarsen, Severin O.
dc.contributor.authorChristiansen, Michael
dc.contributor.authorTheisen, Michael
dc.date.accessioned2013-03-12T17:04:27Z
dc.date.available2013-03-12T17:04:27Z
dc.date.issued2012-09
dc.descriptionThe original publication is available at http://www.plosone.orgen_ZA
dc.description.abstractPlasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub-Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB), was recently shown to correlate with protection from clinical malaria. Human neutrophils constitutively express Fc gamma receptor-FcɣRIIA and FcɣRIIIB by which they interact with immunoglobulin (Ig) G (IgG)-subclass antibodies. Polymorphisms in exon 4 of FCGR2A and exon 3 of FCGR3B genes encoding FcɣRIIA and FcɣRIIIB respectively have been described to alter the affinities of both receptors for IgG. Here, associations between specific polymorphisms, encoding FcɣRIIA p.H166R and FcɣRIIIB-NA1/NA2/SH variants with clinical malaria were investigated in a longitudinal malaria cohort study. FcɣRIIA-p.166H/R was genotyped by gene specific polymerase chain reaction followed by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between FcɣRIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C>A (rs5030738) was significantly associated with protection from clinical malaria under two out of three genetic models (additive: p = 0.0061; recessive: p = 0.097; dominant: p = 0.0076) of inheritance. The FcɣRIIIB-SH allotype (CTGAAA) containing the 233A-allele (in bold) was associated with protection from malaria (p = 0.049). The FcɣRIIIB-NA2*03 allotype (CTGCGA), a variant of the classical FcɣRIIIB-NA2 (CTGCAA) was associated with susceptibility to clinical malaria (p = 0.0092). The present study is the first to report an association between a variant of FcɣRIIIB-NA2 and susceptibility to clinical malaria and provides justification for further functional characterization of variants of the classical FcɣRIIIB allotypes. This would be crucial to the improvement of neutrophil mediated functional assays such as the ADRB assay aimed at assessing the functionality of antibodies induced by candidate malaria vaccines.en_ZA
dc.description.sponsorshipEuropean and Developing Countries Clinical Trials Partnership (www.edctp.org) (TA.2007.40200.012)
dc.description.sponsorshipEuropean Vaccine Initiative (www.euvaccine.eu) (08-2007)
dc.description.sponsorshipAfrican Malaria Network Trust (www.amanet-trust.org) (008/2008AIA)
dc.description.versionPublisher's versionen_ZA
dc.format.extent10 p. : ill.
dc.identifier.citationAdu, B., Dodoo, D., Adukpo, S., Hedley, P.L., Arthur, F.K.N., Gerds, T.A., Larsen, S.O., Christiansen, M. & Theisen, M. 2012. Fc Gamma Receptor IIIB (FcɣRIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Children. PLoS ONE, 7(9): 1-10.en_ZA
dc.identifier.other10.1371/journal.pone.0046197
dc.identifier.urihttp://hdl.handle.net/10019.1/79764
dc.language.isoen_ZAen_ZA
dc.publisherPLOSen_ZA
dc.rights.holderThe authors holds the copyright.en_ZA
dc.subjectFc Gamma Receptor IIIB (FcɣRIIIB) Polymorphismsen_ZA
dc.subjectClinical malaria in children -- Ghana -- Longitudinal studiesen_ZA
dc.subjectPlasmodium falciparum malaria -- Genetic aspectsen_ZA
dc.subjectCerebral malaria in children -- Ghana -- Longitudinal studiesen_ZA
dc.subjectGenetic polymorphisms -- Ghanaen_ZA
dc.subjectFc gamma receptorsen_ZA
dc.subjectNeutrophils -- Immunologyen_ZA
dc.titleFc Gamma Receptor IIIB (FcɣRIIIB) Polymorphisms Are Associated with Clinical Malaria in Ghanaian Childrenen_ZA
dc.typeArticleen_ZA
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