PMID- 28427365 OWN - NLM STAT- MEDLINE DCOM- 20170807 LR - 20181202 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 17 IP - 1 DP - 2017 Apr 20 TI - Association between Fcgamma receptor IIA, IIIA and IIIB genetic polymorphisms and susceptibility to severe malaria anemia in children in western Kenya. PG - 289 LID - 10.1186/s12879-017-2390-0 [doi] LID - 289 AB - BACKGROUND: Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcgammaRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcgammaR polymorphisms influence binding affinity to IgGs and consequently, can influence clinical malaria outcomes. Specifically, variations in FcgammaRIIA -131Arg/His, FcgammaRIIIA-176F/V and FcgammaRIIIB-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 FcgammaRIIA-131Arg/His, FcgammaRIIIA-176F/V and FcgammaRIIIB-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. FcgammaRIIA-131Arg/His and FcgammaRIIIA-176F/V genotypes were determined using TaqMan(R) SNP genotyping, while FcgammaRIIIBNA1/NA2 genotypes were determined using restriction fragment length polymorphism. Hematological and parasitological indices were measured in all study participants. RESULTS: Carriage of FcgammaRIIA-131Arg/FcgammaRIIIA-176F/FcgammaRIIIBNA2 haplotype was associated with susceptibility to SMA (OR = 1.70; 95% CI; 1.02-2.93; P = 0.036), while the FcgammaRIIA-131His/ FcgammaRIIIA-176F/ FcgammaRIIIB 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 FcgammaRIIA-131Arg/His, FcgammaRIIIA-176F/V and FcgammaRIIIB-NA1/NA2 were not associated with susceptibility to SMA. CONCLUSION: The study revealed that haplotypes of FcgammaRs are important in conditioning susceptibility to SMA in immune-naive children from P. falciparum holoendemic region of western Kenya. FAU - Munde, Elly O AU - Munde EO AD - Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya. AD - University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. FAU - Okeyo, Winnie A AU - Okeyo WA AD - Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya. FAU - Raballah, Evans AU - Raballah E AD - University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. AD - Department of Medical Laboratory Science, School of Public Health, Biomedical Sciences and Technology, Masinde Muliro University of Science and Technology, Kakamega, Kenya. FAU - Anyona, Samuel B AU - Anyona SB AD - Department of Medical Biochemistry, School of Medicine, Maseno University, Maseno, Kenya. FAU - Were, Tom AU - Were T AD - Department of Medical Laboratory Science, School of Public Health, Biomedical Sciences and Technology, Masinde Muliro University of Science and Technology, Kakamega, Kenya. FAU - Ong'echa, John M AU - Ong'echa JM AD - University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. AD - Department of Internal Medicine, Centre for Global Health, University of New Mexico, Health Sciences Centre, Albuquerque, New Mexico, USA. FAU - Perkins, Douglas J AU - Perkins DJ AD - University of New Mexico/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. AD - Department of Internal Medicine, Centre for Global Health, University of New Mexico, Health Sciences Centre, Albuquerque, New Mexico, USA. FAU - Ouma, Collins AU - Ouma C AD - Department of Biomedical Sciences and Technology, School of Public Health and Community Development, Maseno University, Maseno, Kenya. collinouma@yahoo.com. AD - Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. collinouma@yahoo.com. AD - African Institute for Development Policy, Nairobi, Kenya. collinouma@yahoo.com. LA - eng GR - D43 TW005884/TW/FIC NIH HHS/United States GR - R01 AI051305/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20170420 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (FCGR3A protein, human) RN - 0 (FCGR3B protein, human) RN - 0 (Fc gamma receptor IIA) RN - 0 (GPI-Linked Proteins) RN - 0 (Receptors, IgG) SB - IM MH - Anemia/etiology/*genetics MH - Child, Preschool MH - Cross-Sectional Studies MH - Female MH - GPI-Linked Proteins/genetics MH - Genetic Predisposition to Disease MH - Genotype MH - Haplotypes MH - Humans MH - Infant MH - Kenya MH - Malaria/*complications/genetics MH - Malaria, Falciparum/blood/complications MH - Male MH - Parasite Load MH - *Polymorphism, Genetic MH - Polymorphism, Restriction Fragment Length MH - Receptors, IgG/*genetics PMC - PMC5397742 OTO - NOTNLM OT - FcgammaRs OT - Malaria anemia OT - Polymorphisms OT - Susceptibility EDAT- 2017/04/22 06:00 MHDA- 2017/08/08 06:00 PMCR- 2017/04/20 CRDT- 2017/04/22 06:00 PHST- 2016/08/17 00:00 [received] PHST- 2017/04/07 00:00 [accepted] PHST- 2017/04/22 06:00 [entrez] PHST- 2017/04/22 06:00 [pubmed] PHST- 2017/08/08 06:00 [medline] PHST- 2017/04/20 00:00 [pmc-release] AID - 10.1186/s12879-017-2390-0 [pii] AID - 2390 [pii] AID - 10.1186/s12879-017-2390-0 [doi] PST - epublish SO - BMC Infect Dis. 2017 Apr 20;17(1):289. doi: 10.1186/s12879-017-2390-0.