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首页> 外文期刊>Infection and immunity >The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations
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The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations

机译：IL17F和IL17RA遗传变异增加两个非洲人群脑疟疾的风险

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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.
机译：脑型疟疾（CM）是恶性疟原虫感染的神经系统并发症，部分由细胞因子介导的炎症引起。尚不清楚调节炎症的白介素-17（IL-17）细胞因子是否能控制CM的发展。为了评估IL-17细胞因子在CM中的参与，我们分析了 IL17A ， IL17F 和 IL17RA （它们编码共同IL-17家族成员的两个受体链）。一项包括115名尼日利亚CM儿童和160名来自社区（CC）的对照的病例对照研究表明， IL17F 参考单核苷酸多态性（SNP）6913472（rs6913472）（ P = 0.004;比值比[OR] = 3.12）， IL17F rs4715291（ P = 0.004; OR = 2.82）， IL17RA rs12159217（ P = 0.01; OR = 2.27）和 IL17RA rs41396547（ P = 0.026; OR = 3.15）与CM独立相关。在240个核心马里家庭三人组（两个父母和一个CM孩子）中进行了复制研究。我们复制了3个SNP的关联，即 IL17F rs6913472（ P = 0.03; OR = 1.39）， IL17RA rs12159217（ P = 0.01; OR = 1.52）和 IL17RA rs41396547（ P = 0.04; OR = 3.50）。我们还发现，尼日利亚和马里的另一种SNP， IL17RA rs41433045，与rs41396547连锁不平衡（LD），与CM相关（ P = 0.002; OR =合并样本中的4.12）。我们排除了 IL17F 和 IL17RA 之外的SNP在强LD中与相关SNP结合的可能性。此外，功能研究的结果表明， IL17F rs6913472的GA基因型加重与较低的IL-17F浓度有关。我们的发现首次显示 IL17F 和 IL17RA 多态性可调节对CM的敏感性，并提供IL-17F可以预防CM的证据。

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