CAJ | 학술논문

[目的]研究HLA-A33表型,TNF-α/TNFRⅡ单核苷酸多态性与肠道病毒71型(EV71)感染遗传易感性的关系,探讨不同基因表型对EV71感染患病风险的影响.[方法]收集2009年9月至2010年10月EV71检测为阳性的急性期中枢神经系统感染患儿123例,根据病情轻重分成轻症组、重症组；提取患儿外周血白细胞的基因组DNA,用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测EV71感染患儿及正常对照儿童HLA-A33表型、TNF-α-308位点的多态性和限制性片段长度多态性-聚合酶链反应(PCR-RFLP)检测TNFRⅡ+196位点的多态性.[结果]EV71感染患儿中HLA-A33表型阳性率(24.39％)与健康儿童组阳性率(11.82％)的差异有统计学意义(x2=6.099,P＜0.05).EV71中枢感染患儿TNF-α-308位点A等位基因频率明显高于正常对照组(x2=6.367,P＜0.05),感染组TNF-α-308GG基因型分布频率显著低于正常对照儿童(x2=5.393,P＜0.05)；而轻症组与重症组相比,其差异无统计学意义(P＞0.05).TNFRⅡ+196位点T等位基因频率在EV71感染组与对照组、轻症组与重症组之间的差异均无统计学意义(P＞0.05).HLA-A33(+)患儿中,EV71感染组TNFRⅡ+196TG基因型频率明显高于正常对照组(x2=3.866,P＜005),而在HLA-A33(-)儿童中,其差异无统计学意义.[结论]HLA-A33表型、TNF-α-308位点基因多态性与EV71中枢感染有关,TNF-α-308GG基因型可能为儿童不易感染EV71的保护基因.TNFRⅡ+196位点基因多态性与EV71感染无关；TNFRⅡ+196TG基因型在一定程度上升高了HLA-A33(+)患儿EV71中枢感染的发病概率.
[목적]연구HLA-A33표형,TNF-α/TNFRⅡ단핵감산다태성여장도병독71형(EV71)감염유전역감성적관계,탐토불동기인표형대EV71감염환병풍험적영향.[방법]수집2009년9월지2010년10월EV71검측위양성적급성기중추신경계통감염환인123례,근거병정경중분성경증조、중증조；제취환인외주혈백세포적기인조DNA,용서렬특이성인물-취합매련반응(PCR-SSP)기술검측EV71감염환인급정상대조인동HLA-A33표형、TNF-α-308위점적다태성화한제성편단장도다태성-취합매련반응(PCR-RFLP)검측TNFRⅡ+196위점적다태성.[결과]EV71감염환인중HLA-A33표형양성솔(24.39％)여건강인동조양성솔(11.82％)적차이유통계학의의(x2=6.099,P＜0.05).EV71중추감염환인TNF-α-308위점A등위기인빈솔명현고우정상대조조(x2=6.367,P＜0.05),감염조TNF-α-308GG기인형분포빈솔현저저우정상대조인동(x2=5.393,P＜0.05)；이경증조여중증조상비,기차이무통계학의의(P＞0.05).TNFRⅡ+196위점T등위기인빈솔재EV71감염조여대조조、경증조여중증조지간적차이균무통계학의의(P＞0.05).HLA-A33(+)환인중,EV71감염조TNFRⅡ+196TG기인형빈솔명현고우정상대조조(x2=3.866,P＜005),이재HLA-A33(-)인동중,기차이무통계학의의.[결론]HLA-A33표형、TNF-α-308위점기인다태성여EV71중추감염유관,TNF-α-308GG기인형가능위인동불역감염EV71적보호기인.TNFRⅡ+196위점기인다태성여EV71감염무관；TNFRⅡ+196TG기인형재일정정도상승고료HLA-A33(+)환인EV71중추감염적발병개솔.
[Objective]To investigate the genetic susceptibility factors of enterovirus71 (EV71) infection by studying the interactions armong HLA-A33 phenotype and TNF-α/TNFR Ⅱ by SNP and the information about the effects of different genes on risk of encephalitis of EV71 infection.[Methods] Reverse transcription polymerase chain reaction(RT-PCR) was used to detect the specific primers of EV71 in the faeces of patients with EV71 infection.Genomic DNA of white blood cell were extracted,then PCR-SSP were used to determine phenotype of HLA-A33 and genotype for the A/G polymorphism at-308 position of TNF-α gene and PCR-RFLP was used to genotype for the T/G polymorphism at + 196 position of TNFR Ⅱ gene.[Results] Compared with that of the normal children,there were obvious statistical significance in E V71 infection patients of the rate of HLA-A33 phenotype (X2=6.099,P ＜ 0.05 ).In EV71 infection groups,the genotype frequency of TNF-α-308GG was significantly lower than that in normal controls( x2=5.393,P ＜ 0.05),and the TNF-α-308 A allele was more common than in nomal group( X2=6.367,P ＜0.05),although there were no obvious statistical significance between mild and critical case groups.There were no obvious statistical significance in the frequencies of TNFR Ⅱ + 196T allele between the patients and control group (P＞0.05).In EV71 group,TG genotype of TNFR Ⅱ + 196 was more common than in control group based on HLA-A33 phenotype( + ) ( X2=3.866,P ＜ 0.05 ).[Conclusions]The polymorphism of HLA-A33,TNF-α-308 single nucleotide may correlate with EV71 infection,maybe TNF-α-308GG is the protective genotype which protect children keep away from EV71.Although there is no obvious statistical significance in EV71 infection patients by SNP,the TNFR Ⅱ + 196(TG)may increase the risk of EV71 infection based on HLA-A33 phenotype( + ).