TOLL样受体2、4mRNA在麻风患者中的表达及其基因多态性研究

发布时间：2018-12-17 01:12

【摘要】：目的研究Toll样受体(Toll-like receptor,TLR)2.4mRNA在麻风患者外周血单个核细胞中的表达及其相关位点(TLR2-597T/C.TLR4-896A/G)基因单核苷酸多态性(single nucleotide polymorphisms, SNP),探讨其与麻风患者免疫的联系以及在麻风感染中的作用机制。方法选择中国贵州毕节地区麻风病例150例,其中瘤型103例,结核样型47例,家族集聚性者43例,非家族集聚性者107例,用RT-PCR法检测麻风患者外周血单个核细胞中TLR2.4mRNA表达水平；用聚合酶链反应限制性片断长度多态性(PCR-RFLP)法分析各样本TLR2 597T/C和TLR4896A/G位点的基因型,比较麻风和正常组基因型分布所占比率以及麻风病例中各组基因型分别占有比率。用SPSS16.0软件的方差分析和X2检验对各组数据进行统计学处理。结果麻风组：TLR2mRNA 0.56±0.06,对照组：0.22±0.10,麻风组：TLR4mRNA 0.34±0.04,对照组：0.21±0.07,TLR2.4mRNA在麻风患者外周血单个核细胞中表达均明显高于对照组(P0.01)。瘤型麻风组：TLR2mRNA 0.62±0.07,TLR4mRNA0.40±0.05;结核样型组：TLR2mRNA 0.43±0.11,TLR4mRNA0.21±0.07;对照组：TLR2mRNA 0.22±0.10,TLR4mRNA 0.21±0.07,TLR2mRNA在瘤型和结核样型麻风中的表达均高于对照组(P0.05),瘤型麻风与结核样型组中的表达相比较未见显著差异(P0.05)；TLR4mRNA在瘤型麻风的表达明显高于对照组(P0.05),在结核样型麻风中的表达与对照组相比未见显著差异(P0.05),在瘤型麻风中的表达明显高于结核样型组(P0.05)。家族集聚性组：TLR2mRNA 0.46±0.12,TLR4mRNA 0.27±0.08;非家族集聚性组：TLR2mRNA 0.60±0.08,TLR4mRNA 0.37±0.05;TLR2. 4mRNA在家族集聚性组与非家族集聚性组中的表达未见显著差异(P0.05)。TLR2(597T/C)TT、TC、CC三种基因型在麻风患者和对照组中的分布频率分别为43.3%、38.7%、18%和48.0%、42.0%、10.0%,无明显差异(P0.05)；瘤型和结核样型TT、TC、CC基因型所占比率分别为41.7%、38.8%、19.5%和46.8%、38.3%、14.9%,差异无统计学意义(P0.05)；家族集聚性和非家族集聚性TT、TC、CC基因型所占比率分别为48.8%、37.2%、14.0%和41.1%、39.3%、19.6%,差异无统计学意义(P0.05)。所有研究对象未检测到TLR4 (896A/G)多态性,基因型均为896AA野生纯合子。结论TLR2、4mRNA在麻风患者外周血单个核细胞中的表达明显升高,提示TLR2、4可能是麻风杆菌的特异识别受体,TLR4可能还在瘤型麻风的发生中起着重要作用,TLR2、4在麻风的发生和病情进展中可能起到了一定的作用。TLR2 (597T/C)、TLR4 (896A/G)多态性与中国贵州毕节地区麻风无相关性。
[Abstract]:Objective to study the expression of Toll like receptor (Toll-like receptor,TLR) 2.4mRNA in peripheral blood mononuclear cells (PBMC) of leprosy patients and the single nucleotide polymorphism (single nucleotide polymorphisms, SNP), (SNP) of TLR2-597T/C.TLR4-896A/G gene. To explore the relationship between leprosy and immunity of leprosy patients and its role in leprosy infection. Methods 150 cases of leprosy in Bijie District, Guizhou Province, China were selected, including 103 cases of tumor type, 47 cases of tuberculous type, 43 cases of familial agglomeration, 107 cases of non-familial agglomeration. The expression of TLR2.4mRNA in peripheral blood mononuclear cells (PBMC) of leprosy patients was detected by RT-PCR assay. The genotypes of TLR2 597T/C and TLR4896A/G loci were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The percentage of genotype distribution in leprosy and normal group and the percentage of genotype in each group were compared. Analysis of variance and X 2 test of SPSS16.0 software were used to deal with the data of each group. Results the expression of TLR2mRNA 0.56 卤0.06 in leprosy group, 0.22 卤0.10 in control group, TLR4mRNA 0.34 卤0.04 in leprosy group and 0.21 卤0.07 TLR2.4 mRNA in peripheral blood mononuclear cells of leprosy patients were significantly higher than those in control group (P0.01). TLR2mRNA 0.62 卤0.07TLR4mRNA0.40 卤0.05in leprosy group, TLR2mRNA 0.43 卤0.11TLR4mRNA0.21 卤0.07in tuberculous type group. In control group, the expression of TLR2mRNA 0.22 卤0.10 TLR4 mRNA 0.21 卤0.07 TLR2 mRNA in leprosy was significantly higher than that in control group (P0.05), but there was no significant difference between tuberculous leprosy group and tumor-type leprosy group (P0.05). The expression of TLR4mRNA in leprosy was significantly higher than that in control group (P0.05), but the expression of TLR4mRNA in tuberculous leprosy was significantly higher than that in tuberculous leprosy (P0.05). Family agglomeration group: TLR2mRNA 0.46 卤0.12 TLR4 mRNA 0.27 卤0.08, TLR2mRNA 0.60 卤0.08 TLR4 mRNA 0.37 卤0.05 TLR2. There was no significant difference in the expression of 4mRNA between familial agglomeration group and non-familial agglomeration group (P0.05). The distribution frequency of TLR2 (597T/C) TT,TC,CC genotype in leprosy patients and control group was 43.3% and 38.7%, respectively. There was no significant difference between 18% and 48.0% and 42.0% and 10.0% (P0.05). The percentage of TT,TC,CC genotypes in tumor type and tuberculous type was 41.7% and 38.5%, respectively, and 38.3% and 46.8% in tuberculous type, respectively. The difference was not statistically significant (P0.05). The percentage of TT,TC,CC genotypes of familial agglomeration and non-familial agglomeration were 48.8% and 41.1%, respectively. There was no significant difference between them (P0.05). No TLR4 (896A/G) polymorphism was detected in all subjects and the genotype was 896AA wild homozygote. Conclusion the expression of TLR2,4mRNA in peripheral blood mononuclear cells of leprosy patients is significantly increased, suggesting that TLR2,4 may be a specific recognition receptor of leprosy, and TLR4 may also play an important role in the pathogenesis of leprosy. TLR2,4 may play a role in the occurrence and progression of leprosy, but TLR2 (597T/C), TLR4 (896A/G) polymorphism is not associated with leprosy in Bijie area, Guizhou, China.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R755

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