精神分裂症患者血浆miRNA筛选验证及RABEP1基因多态性与体重变化的关联研究

发布时间：2018-04-11 08:52

  本文选题：miRNA + 精神分裂症　； 参考：《皖南医学院》2017年硕士论文

【摘要】：目的:对前期芯片筛选出的精神分裂症(Schizophrenia,SZ)患者血浆miRNA异常表达进行重复验证,以期从miRNA角度探讨SZ的发病分子机制;探究RABEP1基因多态性与抗精病药物所致体重变化的关联。方法:在78例首发SZ患者和75例健康对照者中采用实时荧光定量PCR方法验证血浆中miRNA差异性表达,采用ROC曲线分析血浆miRNA用于诊断SZ的价值;调查并随访1701例首发SZ患者使用抗精神病药物治疗2周后的体重变化。使用TaqMan基因分型技术检测RABEP1基因多态性。多元logistic回归分析RABEP1基因与抗精神病药物导致体重变化的关联性。结果:筛选出差异表达miRNA 17种,进一步验证出16种差异表达miRNA(miR-24、miR-146a、mi R-150、miR-197、miR-328、miR-146b、miR-520a-3p、miR-886-5p、miR-320、miR-574-3p、miR-628-3p、miR-1243、mi R-663b、miR-1274a、miR-1274b、miR-664)。ROC曲线结果显示,有5种miRNA(miR-328、miR-886-5p、miR-1243、miR-663b、miR-1274a)对SZ的诊断有较高的意义(均有AUC0.70);RABEP1基因多态性与体重变化的关联分析显示,在总人群中,rs1058398和rs1065482位点相加模型、显性模型、隐性模型均无统计学意义。分层分析显示,校正协变量后,使用阿立哌唑患者中,rs1058398和rs1065482的相加模型及显性模型均与体重增加显著关联,相加模型OR值(95%CI)分别为1.777(1.077-2.934)和2.424(1.236-4.753),P值分别0.025和0.010,显性模型OR值(95%CI)分别为2.182(1.123-4.242)和2.393(1.161-4.929),P值分别0.021和0.018;单一用药组中,rs1058398显性模型与体重降低显著关联,OR值(95%CI)为0.605(0.381-0.961),P值为0.033;联合用药组中,rs1058398显性模型与体重增加存在统计关联,OR值(95%CI)为1.573(1.106-2.237),P值为0.012;在女性人群中,rs1058398显性模型与体重增加显著关联,OR值(95%CI)为1.372(1.002-1.880),P值为0.049;在男性人群中,rs1065482相加模型与体重增加显著关联,OR值(95%CI)为1.408(1.033-1.918),P值为0.030;在年龄35岁人群中rs1065482相加模型与体重增加显著关联,OR值(95%CI)为1.356(1.017-1.809)。结论:miR-24、miR-146a、miR-150、miR-197、miR-328、miR-146b、miR-520a-3p、miR-886-5p、miR-320、miR-574-3p、miR-628-3p、miR-1243、mi R-663b、miR-1274a、miR-1274b、miR-664与SZ存在显著关联;RABEP1基因rs1058398和rs1065482位点与抗精神病药物治疗所致SZ患者体重增加之间的关联受到年龄、性别和抗精神病药物的影响;RABEP1基因变异可能与SZ患者服用阿立哌唑所致体重增加有关。
[Abstract]:Objective: to repeatedly verify the abnormal expression of miRNA in plasma of patients with schizophrenia by microarray screening in order to explore the molecular mechanism of SZ from the point of view of miRNA and to explore the association between RABEP1 gene polymorphism and body weight changes induced by antispermatogenic drugs.Methods: the differential expression of miRNA in plasma was verified by real-time fluorescence quantitative PCR in 78 first-episode SZ patients and 75 healthy controls. The value of plasma miRNA in diagnosis of SZ was analyzed by ROC curve.To investigate and follow up the weight changes of 1701 patients with initial SZ after 2 weeks of antipsychotic therapy.TaqMan genotyping technique was used to detect the polymorphism of RABEP1 gene.Multiple logistic regression analysis showed that RABEP1 gene was associated with weight change induced by antipsychotics.缁撴灉:绛涢，

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