中国汉族人群VEGF基因多态性与帕金森病的相关性研究

发布时间：2018-04-16 06:56

本文选题：VEGF + 帕金森氏病　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:研究表明血管内皮生长因子(vascular endothelial growth factor,VEGF)可以保护多巴胺能神经元,帕金森氏病(Parkinson’s disease,PD)是因为脑黑质纹状体多巴胺能神经元变性导致的进行性神经系统变性疾病。本研究旨在探讨VEGF(rs699947,rs2010963及rs3025039)基因多态性与中国汉族人群散发PD(sporadic PD)易感性之间的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术、基因测序法检测400例中国汉族散发PD患者与400例正常对照者的VEGF(rs699947,rs2010963及rs3025039)的基因型。结果:对于rs699947及rs2010963来说,两位点的基因型和等位基因频率分布在PD组与对照组间无显著差异。且在三种遗传模型下分析及将发病年龄与性别进行各亚组间分析后均未发现有显著的差异。rs3025039位点在PD组与对照组间基因型分布频率上存在显著差异(p=0.035)。PD组的T等位基因显著高于对照组(OR 1.497,95%CI 1.099 2.040,P=0.013)。同时,在加性模型(TT vs.CT vs.CC:OR 1.489,95%CI1.018 2.177,P=0.040)以及显性模型(TT+CT vs.CC:OR 1.538,95%CI 1.068 2.216,P=0.021)均发现rs3025039位点基因多态性与PD易感性存在相关性。在亚组分析中:在男性PD与健康对照组之间的基因型分布频率存在显著差异(P=0.028),除此外,男性PD患者T等位基因频率较对照组显著增加(OR 1.721,95%CI1.148 2.579,P=0.008);在晚发PD(发病年龄大于50岁)与健康对照组之间的基因型分布频率存在显著差异(P=0.006),晚发PD患者T等位基因频率较对照组显著增加(OR 1.678,95%CI 1.217 2.314,P=0.002)。基于性别及早晚发与对照组遗传模型分析中,在男性PD、晚发PD也发现显著相关性。在我们研究的中,由VEGF三位点(rs699947 and rs2010963,D’=0.531,r2=0.073;rs699947 and rs3025039,D’=0.121,r2=0.008;rs2010963 and rs3025039,D’=0.355,r2=0.017)构建的单倍体模型中不存在强连锁不平衡,并且,在PD组与对照组未发现存在统计学意义。结论:VEGF基因可能影响中国汉族人群散发PD的发病,rs3025039位点基因多态性是散发PD(sporadic PD)的危险性因素。
[Abstract]:Objective: it has been shown that vascular endothelial growth factor (VEGF) can protect dopaminergic neurons. Parkinson's disease (PD) is a progressive neurodegenerative disease caused by the degeneration of dopaminergic neurons in the striatum of the substantia nigra.The aim of this study was to investigate the relationship between the polymorphism of VEGF rs699947 rs2010963 and rs302503939 and the susceptibility to sporadic PD(sporadic in Chinese Han population.Methods: polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the genotypes of VEGF rs699947 rs2010963 and rs3025039 in 400 sporadic PD patients of Han nationality and 400 normal controls.Results: for rs699947 and rs2010963, there was no significant difference in genotype and allele frequency distribution between PD group and control group.There was no significant difference in T alleles between PD group and control group after analysis of three genetic models and analysis of onset age and sex among subgroups. Rs3025039 locus had no significant difference between PD group and control group.The OR of the gene was significantly higher than that of the control group (OR 1.497-95).At the same time, it was found that the polymorphism of rs3025039 locus gene was associated with the susceptibility to PD in the additive model TT vs.CT vs.CC:OR 1.489 ~ 95CI1.018 + 2.177P0.040) and the dominant model of TT CT vs.CC:OR 1.53895 CI 1.068 / 2.216P0.021).In subgroup analysis, there was a significant difference in genotype distribution between male PD and healthy controls.The frequency of T allele in male PD patients was significantly higher than that in the control group, and the frequency of T allele was significantly higher in male PD patients than in the control group, and the frequency of T allele in the patients with late onset of PD was significantly different from that in the healthy control group, and the T allele frequency in the patients with late onset of PD was significantly higher than that in the control group, and the frequency of T alleles in the patients with late onset of PD was significantly higher than that in the healthy controls.Compared with the control group, the rate of OR increased significantly, OR 1.67895, CI 1.217 and 2.314P0. 002.Based on the genetic model of sex and early onset and control group, significant correlation was also found between male PD-onset and late-onset PD.In our study, there was no strong linkage imbalance in the single model constructed from the VEGF three-locus rs699947 and / Rs2010963DX 0.531r2n 0.073 rs699947 and rs3025039D0. 008rs2018rs2010063 and rs303355R2O0.017), and no statistical significance was found between the PD group and the control group.Conclusion the polymorphism of rs3025039 gene may be a risk factor for sporadic PD(sporadic in Chinese Han population.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.5

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