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Functional haplotypes of Fc gamma (Fcγ) receptor (FcγRIIA and FcγRIIIB) predict risk to repeated episodes of severe malarial anemia and mortality in Kenyan children.

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dc.contributor.author Ouma, C
dc.contributor.author Davenport, GC
dc.contributor.author Garcia, S
dc.contributor.author Kempaiah, P
dc.contributor.author Chaudhary, A
dc.contributor.author Were, T
dc.contributor.author Anyona, SB
dc.contributor.author Raballah, E
dc.contributor.author Konah, SN
dc.contributor.author Hittner, JB
dc.contributor.author Vulule., JM
dc.contributor.author Ong'echa, JM
dc.contributor.author Perkins, DJ
dc.date.accessioned 2018-01-17T09:34:37Z
dc.date.available 2018-01-17T09:34:37Z
dc.date.issued 2012-02
dc.identifier.citation Ouma, C., Davenport, G. C., Garcia, S., Kempaiah, P., Chaudhary, A., Were, T., … Perkins, D. J. (2012). Functional Haplotypes of Fc gamma (Fcγ) receptor (FcγRIIA and FcγRIIIB) predict risk to repeated episodes of severe malarial anemia and mortality in Kenyan children. Human Genetics, 131(2), 289–299. http://doi.org/10.1007/s00439-011-1076-8 en_US
dc.identifier.uri https://repository.maseno.ac.ke/handle/123456789/123
dc.description.abstract Development of protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG to Fc gamma (γ) receptors. Variation in human FcγRIIA-H/R-131 and FcγRIIIB-NA1/NA2 affect differential binding of IgG sub-classes. Since variability in FcγR may play an important role in severe malarial anemia (SMA) pathogenesis by mediating phagocytosis of red blood cells and triggering cytokine production, the relationship between FcγRIIA-H/R131 and FcγRIIIB-NA1/NA2 haplotypes and susceptibility to SMA (Hb<6.0g/dL) was investigated in Kenyan children (n=528) with acute malaria residing in a holoendemic P. falciparum transmission region. In addition, the association between carriage of the haplotypes and repeated episodes of SMA and all-cause mortality were investigated over a three-year follow-up period. Since variability in FcγR can alter interferon (IFN)-γ production, a mediator of innate and adaptive immune responses, functional associations between the haplotypes and IFN-γ were also explored. During acute malaria, children with SMA had elevated peripheral IFN-γ levels (P=0.006). Although multivariate logistic regression analyses (controlling for covariates) revealed no associations between the FcγR haplotypes and susceptibility to SMA during acute infection, the FcγRIIA-131H/FcγRIIIB-NA1 haplotype was associated with decreased peripheral IFN-γ (P=0.046). Longitudinal analyses showed that carriage of the FcγRIIA-131H/FcγRIIIB-NA1 haplotype was associated with reduced risk of SMA (RR; 0.65, 95%CI, 0.46-0.90; P=0.012) and all-cause mortality (P=0.002). In contrast, carriers of the FcγRIIA-131H/FcγRIIIB-NA2 haplotype had increased susceptibility to SMA (RR; 1.47, 95%CI, 1.06-2.04; P=0.020). Results here demonstrate that variation in the FcγR gene alters susceptibility to repeated episodes of SMA and mortality, as well as functional changes in IFN-γ production. en_US
dc.language.iso en en_US
dc.publisher Pub Med Central en_US
dc.subject FcγR en_US
dc.subject alciparum en_US
dc.subject SMA en_US
dc.subject mortality en_US
dc.subject children en_US
dc.title Functional haplotypes of Fc gamma (Fcγ) receptor (FcγRIIA and FcγRIIIB) predict risk to repeated episodes of severe malarial anemia and mortality in Kenyan children. en_US
dc.type Article en_US


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