基于microRNA差异表达的精神分裂症与抑郁症共病研究

摘要

目的 观察精神分裂症(SZ)患者中差异表达的microRNA(miRNA),从miRNA表达水平上分析SZ与抑郁症的关系.方法 通过基因芯片筛选在SZ患者中差异表达的miRNA.采用实时定量PCR(qRT-PCR)在40例SZ患者外周血单核细胞中验证芯片筛查结果,并进行精神分裂症阳性和阴性症状量表(队NSS)评定,同时检测抑郁症中差异表达的5种miRNA(miR-1972、miR-26b、miR-4485、miR-4498、miR-4743)的表达改变及其与SZ中差异表达的miRNA及PANSS评分的相关性.结果 与正常人相比,SZ患者中33种miRNA存在差异表达(32种表达上调,1种表达下调),且其中8种上调的miRNA(miR-1273d、miR-1303、miR-3064-5p、miR-3131、miR-3687、miR-4428、miR-4725-3p、miR-5096)表达差异有统计学意义(P＜0.05).在抑郁症中差异表达的5种miRNA在SZ患者中差异表达也有统计学意义(P＜0.05),且与SZ中差异表达的8种miRNA呈中、高度相关(r=0.607～0.909,P＜0.01),其中miR-1972与PANSS量表阳性症状得分呈显著正相关(r=0.339,P＜0.05),miR-26b与复合量表因子分呈显著正相关(r=0.342,p＜0.05).结论 SZ与抑郁症不仅具有某些共同的临床表现,二者在分子遗传学方面也可能有共同的病理基础.%Objective To investigate the differential expression of microRNA (miRNA) in schizophrenia (SZ) patients,and explore the comorbidity of SZ and depression disorder based upon miRNA expression.Methods Affymetrix array analysis was used to investigate the differentially expressed miRNA in SZ patients firstly,and then quantitative real-time polymerase chain reaction (qRT-PCR) was further carried out to confirm the selected miRNA in peripheral blood mononuclear cells of 40 SZ patients,whom were administered by Positive and Negative Syndrome Scale (PANSS) and the selected miRNAs in depression disorder patients has also been confirmed by Affymetrix array analysis and qRT-PCR in our previous studies.Results Affymetrix array analysis indicated that there existed 33 miRNAs which differentially expressed (32 up-regulated and 1 down-regulated) compared with normal controls.qRT-PCR results suggested that the expression of 8 miRNAs (miR-1273d,miR-1303,miR-3064-5p,miR3131,miR-3687,miR-4428,miR-4725-3p and miR-5096) were significantly up-regulated in SZ;the miRNA differentially expressed in depression disorder patients also had differential expression in SZ patients (P＜0.05).There were significant correlation between the miRNAs differentially expressed in depression disorder patients and in SZ patients (P＜0.01).MiR-1972 differentially expressed in depression disorder patients had significant positive correlation with the positive symptoms of PANSS (P＜0.05),and miR-26b was positively correlated with composite factor (P＜0.05).Conclusion Comorbidity of SZ and depression disorder is observed not only on the clinical symptoms,but on the molecular genetic basis.