Dataset Information

Association between Fc? receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.

ABSTRACT:

Background

Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (Fc?Rs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. Fc?R polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in Fc?RIIA -131Arg/His, Fc?RIIIA-176F/V and Fc?RIIIB-NA1/NA2 modulate immune responses through altered binding preferences to IgGs and immune complexes. Differential binding, in turn, changes ability of immune cells to respond to infection through production of inflammatory mediators during P. falciparum infection.

Methods

We determined the association between haplotypes of Fc?RIIA-131Arg/His, Fc?RIIIA-176F/V and Fc?RIIIB-NA1/NA2 variants and severe malarial anemia (SMA; hemoglobin < 6.0 g/dL, any density parasitemia) in children (n = 274; aged 6-36 months) presenting for their first hospital visit with P. falciparum malaria in a holoendemic transmission region of western Kenya. Fc?RIIA-131Arg/His and Fc?RIIIA-176F/V genotypes were determined using TaqMan® SNP genotyping, while Fc?RIIIBNA1/NA2 genotypes were determined using restriction fragment length polymorphism. Hematological and parasitological indices were measured in all study participants.

Results

Carriage of Fc?RIIA-131Arg/Fc?RIIIA-176F/Fc?RIIIBNA2 haplotype was associated with susceptibility to SMA (OR = 1.70; 95% CI; 1.02-2.93; P = 0.036), while the Fc?RIIA-131His/ Fc?RIIIA-176F/ Fc?RIIIB NA1 haplotype was marginally associated with enhanced susceptibility to SMA (OR: 1.80, 95% CI; 0.98-3.30, P = 0.057) and higher levels of parasitemia (P = 0.009). Individual genotypes of Fc?RIIA-131Arg/His, Fc?RIIIA-176F/V and Fc?RIIIB-NA1/NA2 were not associated with susceptibility to SMA.

Conclusion

The study revealed that haplotypes of Fc?Rs are important in conditioning susceptibility to SMA in immune-naive children from P. falciparum holoendemic region of western Kenya.

SUBMITTER: Munde EO

PROVIDER: S-EPMC5397742 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Association between Fcγ receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya.

Munde Elly O EO Okeyo Winnie A WA Raballah Evans E Anyona Samuel B SB Were Tom T Ong'echa John M JM Perkins Douglas J DJ Ouma Collins C

BMC infectious diseases 20170420 1

<h4>Background</h4>Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcγRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcγR polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in FcγRIIA -131Arg/His, FcγRIIIA-176F/V and FcγRIIIB-NA1/NA2 modulate i ...[more]

PMID: 28427365

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