慢阻肺患者PTX3基因多态性与曲霉感染易感性的关系

发布时间：2018-06-30 18:42

本文选题：PTX3 + 基因多态性　；参考：《南方医科大学》2017年硕士论文

【摘要】：第一章慢阻肺患者PTX3基因多态性与曲霉易感性的关系目的探索慢阻肺患者合并曲霉感染是否与PTX3基因多态性有关。方法采用病例对照研究,收集2015年1月至2016年11月南京军区南京总医院呼吸科就诊的慢阻肺患者共173例,其中伴有曲霉感染患者36例,单纯慢阻肺患者137例,记录详细的临床资料。采集患者外周血约2ml,提取DNA样本。采用直接测序法分析 PTX3 基因rs2305619、rs3816527、rs1840680、rs3845978多态性。结果单纯慢阻肺组与慢阻肺合并曲霉感染组患者之间性别、年龄、吸烟史、激素使用史、慢阻肺严重程度之间差异无统计学意义。PTX3基因4个SNP点中,3个SNP位点符合哈温平衡(rs2305619,rs3816527,rs1840680)。合并曲霉组rs1840680中的A等位基因频率高于慢阻肺组。差异有统计学意义(p=0.008)。并且在隐形模型中,合并曲霉组AA基因型频率高于慢阻肺组(p=0.00003)。rs2305619,rs3816527位点等位基因频率和基因型频率在两组之间差异均无统计学意义。单倍型分析显示rs2305619,rs3816527构成的三种单倍型(G-A;A-A;A-C)在两组间的分布频率无明显差异。结论PTX3基因中rs1840680多态性与慢阻肺合并曲霉感染发生有关:相比AG、GG基因型,AA基因型是曲霉感染发生的危险因素。而rs2305619,rs3816527两种SNP位点多态性与曲霉感染相关性尚不明确。其中rs2305619,rs3816527构成的单倍型与慢阻肺合并曲霉感染的相关性尚不明确。第二章不同PTX3基因型的慢阻肺患者血浆PTX3水平与曲霉感染发生的相关性目的探索在不同基因型慢阻肺患者中血浆PTX3水平的变化,以及血浆PTX3水平与慢阻肺患者曲霉感染的相关性。方法采用病例对照研究,选取上述已收集的173名患者。将患者分为慢阻肺稳定组、慢阻肺急性加重组和慢阻肺合并曲霉组。采集患者外周循环血约2ml。分离血浆及血细胞,留取血浆样本,采用酶联免疫吸附实验测定血浆中PTX3水平。结果在慢阻肺稳定组中,不同肺功能分级慢阻肺患者血浆PTX3水平之间差异无统计学意义。合并曲霉感染组与慢阻肺稳定组及慢阻肺急性加重组相比,血浆PTX3水平均明显升高;而在慢阻肺稳定组和慢阻肺急性加重组之间血浆PTX3水平无明显差异。将患者根据rs1840680多态性进行分型。在曲霉感染组,AA基因型血浆PTX3水平显著低于AG/GG基因型。结论血浆PTX3水平不受COPD患者肺功能严重程度影响。曲霉感染患者血浆PTX3水平显著高于单纯慢阻肺患者,提示血浆PTX3检测有潜在可能作为慢阻肺合并肺曲霉病的血清标志物。在合并曲霉感染患者中,rs1840680AA基因型患者血浆PTX3水平明显低于AG/GG基因型患者,进一步证实携带rs1840680 AA基因型患者是曲霉感染发生的危险因素。
[Abstract]:Chapter 1 relationship between PTX3 gene polymorphism and susceptibility to Aspergillus in patients with COPD objective to explore whether the association of PTX3 gene polymorphism with Aspergillus mutans infection in COPD patients. Methods from January 2015 to November 2016, 173 patients with chronic obstructive pulmonary disease (COPD), 36 patients with aspergillus infection and 137 patients with simple COPD, were collected from the respiratory department of Nanjing General Hospital of Nanjing military region from January 2015 to November 2016. Record detailed clinical data. About 2 ml of peripheral blood was collected and DNA samples were extracted. The polymorphism of PTX3 gene rs2305619rs3816527 rs1840680 rs3845978 was analyzed by direct sequencing. Results there was no significant difference in sex, age, history of smoking, history of hormone use and severity of chronic obstructive pulmonary disease between patients with chronic obstructive pulmonary disease (COPD) and chronic obstructive pulmonary disease (COPD). There was no significant difference among the four SNP sites of PTX3 gene. Three SNP loci were in accordance with Haven balance (rs2305619rs3816527rs1840680). The frequency of A allele in rs1840680 in Aspergillus group was higher than that in COPD group. The difference was statistically significant (p0. 008). In the invisible model, the frequency of AA genotype in the combined aspergillus group was higher than that in the chronic obstructive pulmonary group (p0. 00003). The allele frequency and genotype frequency of rs2305619rs3816527 were not significantly different between the two groups. Haplotype analysis showed that there was no significant difference in the distribution frequency between the two groups of the three haplotypes of rs2305619 (rs3816527). Conclusion rs1840680 polymorphism in PTX3 gene is associated with Aspergillus mutans infection in COPD. Compared with AGG genotype AA genotype is a risk factor for Aspergillus infection. However, the association between the two SNP loci polymorphism and Aspergillus infection was not clear. The haplotypes of rs2305619 rs3816527 and the relationship between Rs2305619 and COPD complicated with Aspergillus sp. Chapter 2 the relationship between plasma PTX3 levels and aspergillus infection in patients with COPD with different PTX3 genotypes objective to explore the changes of plasma PTX3 levels in patients with different genotypes of COPD. And the correlation between plasma PTX 3 level and Aspergillus mutans infection in patients with chronic obstructive pulmonary disease (COPD). Methods 173 patients were selected by case-control study. The patients were divided into stable COPD group, acute COPD plus recombination group and COPD with aspergillus group. Peripheral circulation blood was collected about 2 ml. Plasma and blood cells were isolated, plasma samples were collected and plasma PTX3 levels were measured by enzyme linked immunosorbent assay (Elisa). Results in the stable COPD group, there was no significant difference in plasma PTX3 levels among patients with different pulmonary function grades. The levels of plasma PTX3 in patients with Aspergillus mutans infection were significantly higher than those in patients with chronic obstructive pulmonary stability (COPD) and chronic obstructive pulmonary disease (COPD), but there was no significant difference in plasma PTX3 levels between COPD group and COPD group. The patients were classified according to rs1840680 polymorphism. The plasma PTX3 level of AA genotype in Aspergillus group was significantly lower than that of AGR GG genotype. Conclusion Plasma PTX 3 level is not affected by the severity of pulmonary function in COPD patients. The level of plasma PTX3 in patients with Aspergillus mutans infection was significantly higher than that in patients with chronic obstructive pulmonary disease, suggesting that the detection of plasma PTX3 might be a potential serum marker for COPD complicated with pulmonary aspergillosis. In patients with Aspergillus infection, the plasma PTX3 level in patients with rs1840680AA genotype was significantly lower than that in patients with AGP-GG genotype. It was further confirmed that patients with rs1840680 AA genotype were risk factors of Aspergillus infection.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.9

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