Skip to Main content Skip to Navigation
Journal articles

The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

Abstract : 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.
Document type :
Journal articles
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-01595971
Contributor : Lionel Spinelli Connect in order to contact the contributor
Submitted on : Wednesday, September 27, 2017 - 10:23:39 AM
Last modification on : Tuesday, May 17, 2022 - 2:58:09 PM

Links full text

Identifiers

Collections

Citation

S. Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Sandrine Cabantous, et al.. The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations. Infection and Immunity, American Society for Microbiology, 2016, 84 (2), pp.590-597. ⟨10.1128/IAI.00671-15⟩. ⟨hal-01595971⟩

Share

Metrics

Record views

30