摘要
目的探讨TLR7基因单核苷酸多态性（SNP）与肠道病毒71（EV71）型感染的相关性及其产生的机制。方法应用TaqMan探针基因分型技术，对775例EV71感染者（轻症439例，重症336例）和748名健康对照SNP位点rs179019和rs3853839进行基因分型，比较其等位基因频率的差异；检测相关SNP位点不同基因型携带者PBMC中TLR7 mRNA、α干扰素和IL-6表达水平。基因频率采用Logistic回归分析。结果重症组女性rs3853839基因型GC和CC的频率明显高于轻症组（rs3853839 GC：OR＝0.36，95%CI为0.14～0.82, P＝0.01；rs3853839 CC：OR＝0.19，95%CI为0.11～0.69，P＝0.01）。重症组男性rs3853839基因型C的频率也明显高于轻症组（OR＝0.35，95%CI为0.19～0.63, P＝0.01）。rs3853839基因型CC女性携带者TLR7 mRNA水平明显低于基因型GC和GG（CC比GG：P＝0.005；CC比GC：P＝0.016），rs3853839基因型C男性携带者也低于其基因型G（C比G：P＝0.004）；TLR7激动剂的刺激下，rs3853839基因型CC的女性携带者PBMC中α干扰素表达水平明显低于基因型GG和GC（CC比GG：P＝0.001；CC比GC：P＝0.011），而其IL-6表达水平也明显低于基因型GG和GC（CC比GG：P＝0.001；CC比GC：P＝0.026）；男性rs3853839的基因型C携带者α干扰素和IL-6表达水平均明显低于基因型G携带者（α干扰素：P＝0.003；IL-6：P＝0.018）。结论TLR7基因rs3853839等位基因C是儿童EV71重度感染的危险因素，可能与其特异的细胞因子表达水平有关。
Objective To explore the association between tollqike receptor 7 （TLR7） single nucleotide polymorphisms （SNP） and susceptibility of hand, foot and mouth disease caused by enterovirus （EV）71 infection. Methods The genotype of SNP （rs179019 and rs3853839） was determined in 775 EV71-infected cases （including 439 mild cases and 336 severe cases） and 748 healthy control cases with TaqMan assay. The difference of allele frequencies was compared. The difference of TLR7 mRNA expression in peripheral blood mononuclear cells （PBMCs） derived from different SNP genotype carriers was detected. PBMCs derived from different SNP genotype carriers were stimulated by imiquimod and the TLR7-specific interferon-α（IFN-α） and interleukin-6 （IL-6） secretions were detected. Logistic regression was used to analyze for genotype frequency. Results The frequencies of rs3853839 genotype CC and CG in female patients of severe group were significantly higher than mild group （rs3853839 GC： OR= 0.36, 95%CI：0.14-0.82, P=0.01;rs3853839 CC： OR=0. 19,95%CI：0. 11-0. 69,P=0.01）. In addition, the frequency of rs3853839 genotype C in severe male group was significantly higher compared with that in mild group （OR=0.35,95% CI： 0. 19 - 0. 63, P = 0.01）. Female carriers with rs3853839 genotype CC had significantly lower TLR7 mRNA expression than genotype GC and GG （CC vs GG： P=0. 005; CC vs GC： P= 0. 016）. Male carriers with rs3853839 genotype C also had significantly lower TLR7 mRNA expression than genotype G （C vs G： P=0. 004）. After stimulation of imiquimod, the expression of IFN- α （CC vs GG, P=0. 001% CC vs GC： P=0. 026） and IL-6 productions （CC vs GG： P=0. 001; CC vs GC： P= 0. 011） were significantly lower in female carriers with rs3853839 genotype CC. The same patterns were observed in male carriers with rs3853839 genotype CC （IFN-α： P= 0. 003; IL-6： P= 0. 018）. Conclusions The rs3853839C allele is the risk factor of severe infection of EV71, which may be due to
作者
张玉琳
竺李莉
张京
李志锋
Zhang Yulin Zhu Lili Zhang Jing Li Zhifeng(Depatment of Human Morphology, School of Medicine and Technology, Ningbo 315100, China)
出处
《中华传染病杂志》
CAS
CSCD
北大核心
2017年第1期39-43,共5页
Chinese Journal of Infectious Diseases
