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Lookup NU author(s): Dr Florence Burte
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Cerebral malaria (CM) is a neurological complication of infection with Plasmodium falciparum that is partly caused by cytokine-mediated inflammation. It is not known whether interleukin-17 (IL-17) cytokines, which regulate inflammation, control the development of CM. To evaluate the involvement of IL-17 cytokines in CM, we analyzed 46 common polymorphisms in IL17A, IL17F, and IL17RA (which encodes the common receptor chain of the members of the IL-17 family) in two independent African populations. A case-control study involving 115 Nigerian children with CM and 160 controls from the community (CC) showed that IL17F reference single nucleotide polymorphism (SNP) 6913472 (rs6913472) (P = 0.004; odds ratio [OR] = 3.12), IL17F rs4715291 (P = 0.004; OR = 2.82), IL17RA rs12159217 (P = 0.01; OR = 2.27), and IL17RA rs41396547 (P = 0.026; OR = 3.15) were independently associated with CM. A replication study was performed in 240 nuclear Malian family trios (two parents with one CM child). We replicated the association for 3 SNPs, IL17F rs6913472 (P = 0.03; OR = 1.39), IL17RA rs12159217 (P = 0.01; OR = 1.52), and IL17RA rs41396547 (P = 0.04; OR = 3.50). We also found that one additional SNP, IL17RA rs41433045, in linkage disequilibrium (LD) with rs41396547, was associated with CM in both Nigeria and Mali (P = 0.002; OR = 4.12 in the combined sample). We excluded the possibility that SNPs outside IL17F and IL17RA, in strong LD with the associated SNPs, could account for the observed associations. Furthermore, the results of a functional study indicated that the aggravating GA genotype of IL17F rs6913472 was associated with lower IL-17F concentrations. Our findings show for the first time that IL17F and IL17RA polymorphisms modulate susceptibility to CM and provide evidence that IL-17F protects against CM.
Author(s): Marquet S, Conte I, Poudiougou B, Argiro L, Cabantous S, Dessein H, Burté F, Oumar AA, Brown BJ, Traore A, Afolabi NK, Barry A, Omokhodion S, Ndoumbe UE, Shokunbi WA, Sodeinde O, Doumbo O, Fernandez-Reyes D, Dessein AJ
Publication type: Article
Publication status: Published
Journal: Infection and Immunity
Year: 2016
Volume: 84
Issue: 2
Pages: 590-597
Print publication date: 01/02/2016
Online publication date: 14/12/2015
Acceptance date: 23/11/2015
ISSN (print): 0019-9567
ISSN (electronic): 1098-5522
Publisher: American Society for Microbiology
URL: http://dx.doi.org/10.1128/IAI.00671-15
DOI: 10.1128/IAI.00671-15
PubMed id: 26667835
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