IL-10，IL-18基因多态性与中国汉族人群散发性帕金森病相关性研究

发布时间：2018-06-28 20:59

本文选题：帕金森病 + IL-10　；参考：《中南大学》2014年硕士论文

【摘要】：背景：帕金森病(Parkinson's disease, PD)是一种复杂的神经退行性疾病,其发病机制仍不十分明确,主要病理特征是黑质多巴胺能神经元的丢失和神经元胞浆中嗜酸性包涵体(Lewy body)的出现。黑质多巴胺能神经元的丢失通常与神经胶质细胞反应,尤其与小胶质细胞活化有关,并引起细胞因子和趋化因子的高表达。最近越来越多的研究证据表明,神经炎症在PD发病过程中起重要作用,国内外研究发现位于炎性细胞因子启动子区域的单核苷酸多态性(single nucleitide polymorphism, SNP)可增加PD发病的风险性,炎症因子可能与PD患者认知功能障碍有关,并且目前尚无炎症因子多态性与异动症的相关性研究。目的：在中国汉族人群散发性帕金森病(sporadic Parkinson's disease,SPD)及正常对照中对IL-10基因rs1800872 rs1800871, IL-18基因rs187238等三个单核苷酸多态位点进行分析,探讨上述基因多态性与中国汉族SPD易感性的关联,并分析上述3个多态位点可能与PD认知功能障碍(可分为帕金森病痴呆(Dementia in PD, PD-D)和帕金森病轻度认知功能障碍(Mild cognitive impairment in PD, PD-MCI))和异动症(levodopa-induced dyskinesias, LID)的易感性关联。方法：采用飞行时间质谱分析的方法,检测了中国汉族人群464例散发性PD患者(其中包括98例PD-LID,100例PDD,76例PD-MCI)以及477例正常对照者IL-10基因rs1800872、rs1800871, IL-18基因rs187238三个核苷酸位点多态性,使用卡方检验、二分类Logistic回归法比较病例组及正常对照组基因型及等位基因分布频率差异。结果： 1.SPD组rs1800871.rs1800872.rs187238位点的基因型、等位基因频率分布与正常对照组比较差异无显著性(rs1800871位点基因型：χ2=0.948,P=0.622；等位基因频率：x2=0.168,P=0.681.rs1800872位点基因型：χ2=1.316,P=0.518；等位基因频率：χ2=0.363,P=0.547。rs187238位点基因型：χ2=2.698,P=0.260；等位基因频率：χ2=0.312,P=0.577)。对年龄、性别分层分析,3个多态基因型、等位基因比较差异仍无显著性。 2.在PDD和PD-MCI及PD非认知功能障碍患者中比较,3个多态基因型、等位基因比较差异无显著性。 3.在PD-LID和PD-非LID中比较,3个多态基因型、等位基因比较差异无显著性。结论：1.IL-10基因rs1800871.rs1800872与IL-18基因rs187238位点多态性可能与中国汉族人群散发性帕金森病的发病不相关。2.上述3个多态位点多态性可能与PD认知功能障碍和PD异动症的发病不相关。
[Abstract]:Background: Parkinson's disease (PD) is a complex neurodegenerative disease. Its pathogenesis is still unclear. The main pathological features are the loss of dopaminergic neurons in the substantia nigra and the occurrence of eosinophilic body in the cytoplasm of the neurons. The loss of dopaminergic neurons in the substantia nigra is usually associated with the glial reaction, especially the activation of microglia, and the overexpression of cytokines and chemokines. Recently, more and more studies have shown that neuroinflammation plays an important role in the pathogenesis of PD. It has been found that single nucleotide polymorphisms (SNPs) located in the promoter region of inflammatory cytokines (SNPs) can increase the risk of PD. Inflammatory factors may be associated with cognitive impairment in PD patients, and there is no correlation between inflammatory factor polymorphism and dyskinesia. Objective: to analyze three single nucleotide polymorphisms (SNPs) of IL-10 gene rs1800872 rs1800871 and IL-18 gene rs187238 in Chinese Han population with sporadic Parkinson's disease (SPD) and normal controls. The above three polymorphic loci were analyzed to be associated with the susceptibility of PD cognitive dysfunction (including PD in PD-D, mild cognitive impairment in PD (PD-MCI) and levodopa-induced dyskinesias (lid). Methods: three nucleotide polymorphisms of IL-10 gene rs1800872rs1800871 and IL-18 gene rs187238 were detected in 464 sporadic PD patients (including 98 cases of PD-LIDN 100 cases of PD-MCI) and 477 normal controls by time-of-flight mass spectrometry (TF-MS). The frequency of genotype and allele distribution in patients and normal controls were compared by using Chi-square test and two-class logistic regression method. Results: 1. There was no significant difference in genotype and allele frequency distribution of rs1800871.rs1800872.rs187238 locus between SPD group and normal control group (rs1800871 genotype: 蠂 2 + 0.948% P0. 622; allele frequency:% x2 + 0. 168% P = 0. 681.rs1800872: 蠂 2 = 1. 316P0. 518; Allelic frequency: 蠂 ~ 2 ~ (2 +) 0.363 (P) 0.547.rs 187238 genotype: 蠂 ~ (2) 2.698 (P) 0.260; allele frequency: 蠂 ~ (2 +) 0.312 (P ~ (1) 0.77). For age, sex stratification analysis, three polymorphic genotypes and alleles, there was still no significant difference. 2. 2. There was no significant difference among three polymorphic genotypes and alleles among PDD, PD-MCI and PD patients with non-cognitive impairment. Compared with PD-LID and PD-NLID, there was no significant difference in alleles among the three polymorphic genotypes. Conclusion the polymorphism of rs1800871.rs1800872 and rs187238 loci of IL-10 gene and IL-18 gene may not be associated with sporadic Parkinson's disease in Chinese Han population. The polymorphism of these three polymorphic loci may not be associated with PD cognitive dysfunction and PD dyskinesia.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

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