缺血性脑卒中CARD8 rs2043211和NLRP3 rs10754558的遗传共关联作用  

Genetic association of CARD8 rs2043211 with NLRP3 rs10754558 in ischemic stroke

作　　者：吕洁[1] 蒋晓山[2] 谭超 张晶[1] 彭湘晖[1] 林红梅 LYU Jie;JIANG Xiaoshan;TAN Chao;ZHANG Jing;PENG Xianghui;LIN Hongmei(Department of Neurology, the Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin 541002,China)

机构地区：[1]广西壮族自治区南溪山医院神经内科,桂林541002 [2]广西壮族自治区桂林医学院细胞信号转导实验室 [3]广西壮族自治区桂林医学院公共卫生学院

出　　处：《中国神经精神疾病杂志》2019年第5期276-282,共7页Chinese Journal of Nervous and Mental Diseases

基　　金：桂林市科学研究与技术开发计划项目(编号:20170109-30)

摘　　要：目的旨在探索Nod样受体蛋白3(nodlike receptor protein 3,NLRP3)炎症小体组分基因胱天蛋白酶募集域蛋白8(caspase recruitment domain- containing protein 8,CARD8)rs2043211及NLRP3 rs10754558的组合多态性是否会影响中国汉族人群缺血性脑卒中的遗传易感性。方法依据改良的急性卒中治疗Org10172试验(trial of org10172 in acute stroke treatment,TOAST)病因分型诊断标准,将动脉粥样硬化血栓型(n=145)及小动脉型(n=89)缺血性脑卒中纳入本研究,收集对照组115例,应用TaqMan MGB RT-PCR技术进行基因分型,以logistic回归分析基因-基因间的交互作用。结果 NLRP3 rs10754558或CARD8 rs2043211单一基因的小等位基因及基因型频率,在脑梗死两个亚组中的分布,与对照组比较均无统计学差异(P>0.05);logistic回归分析发现,rs10754558的CG基因型与rs2043211的AT基因型在动脉粥样硬化血栓型缺血性卒中的发病中存在交互作用,并增加发病风险(P<0.01,OR=4.95,95%CI:1.69~14.51)。结论 NLRP3炎症小体组分基因的基因型组合CARD8 rs2043211/NLRP3 rs10754558 AT/CG是动脉粥样硬化血栓型缺血性脑卒中的危险因素。Objective To investigate whether the combined polymorphisms in genes encoding the Nodlike Receptor Protein 3(NLRP3)inflammasome components NLRP3 and caspase recruitment domain-containing protein 8(CARD8)affect the genetic susceptibility to ischemic stroke in Chinese Han population. Methods Based on the modified TOAST etiology classification criteria, two subtypes of ischemic stroke, atherosclerotic thrombosis (AT, n=145)and small artery disease (SAD, n=89), were included in this study. All the patients and controls (n=115) were genotyped for CARD8 rs2043211 and NLRP3 rs10754558 using TaqMan SNP assays. Logistic regression was used to test for interactions between CARD8 and NLRP3. Results No significant difference was found in the distribution of the minor allele frequency and genotype frequency of NLRP3 rs10754558 or CARD8 rs2043211 in subtypes of ischemic stroke compared with the control group (P>0.05). Logistic regression association analysis revealed that the genotypic combination CARD8 rs2043211/NLRP3 rs10754558 AT/CG was significantly associated are more likely to suffer from AT subtype ischemic stroke.

关 键 词：缺血性脑卒中 NLRP3炎症小体 CARD8rs2043211 NLRP3rs10754558 

分 类 号：R743.32[医药卫生—神经病学与精神病学] R392.2[医药卫生—临床医学]