Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis
Genetic variation in inflammasome genes is associated with outcome in bacterial meningitis
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DOI：
10.1007/s00251-012-0653-x
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发表时间：
2013-01-01
期刊：
影响因子：
3.2
通讯作者：
van de Beek, Diederik
中科院分区：
文献类型：
--
作者：
Geldhoff, Madelijn;Mook-Kanamori, Barry B.;van de Beek, Diederik
细菌性脑膜炎是一种严重和致命的疾病，最常见的是由肺炎链球菌引起的。疾病结局与蛛网膜下腔炎症反应的严重程度相关。炎性小体是促成这种炎症反应的细胞内信号传导复合物。炎性小体基因的遗传变异在细菌性脑膜炎中的作用在很大程度上是未知的。在一项前瞻性的全国性肺炎球菌脑膜炎患者队列中，我们进行了一项遗传关联研究，发现炎性小体基因CARD 8（rs 2043211）和NLRP 1（rs 11621270）的单核苷酸多态性与疾病预后不良相关。脑脊液中炎性小体相关细胞因子白细胞介素（IL）-1 β和IL-18的水平也与临床结果相关，但与CARD 8和NLRP 1多态性无关。我们的研究结果暗示了炎症体基因的遗传变异在细菌性脑膜炎患者炎症反应和临床结局的调节中的重要作用。
Bacterial meningitis is a severe and deadly disease, most commonly caused by Streptococcus pneumoniae. Disease outcome has been related to severity of the inflammatory response in the subarachnoid space. Inflammasomes are intracellular signaling complexes contributing to this inflammatory response. The role of genetic variation in inflammasome genes in bacterial meningitis is largely unknown. In a prospective nationwide cohort of patients with pneumococcal meningitis, we performed a genetic association study and found that single-nucleotide polymorphisms in the inflammasome genes CARD8 (rs2043211) and NLRP1 (rs11621270) are associated with poor disease outcome. Levels of the inflammasome associated cytokines interleukin (IL)-1 beta and IL-18 in cerebrospinal fluid also correlated with clinical outcome, but were not associated with the CARD8 and NLRP1 polymorphisms. Our results implicate an important role of genetic variation in inflammasome genes in the regulation of inflammatory response and clinical outcome in patients with bacterial meningitis.