双相情感障碍躁狂发作患者线粒体功能相关基因表达分析

Expression of genes related to mitochondrial function in patients with manic episodes of bipolar disorder

目的:探索双相情感障碍躁狂发作患者线粒体功能相关基因的表达特征及差异表达基因与临床代谢指标的相关性。方法:纳入20例双相情感障碍躁狂发作患者(患者组)和20名健康对照者(对照组),采用实时荧光定量PCR(quantitative real-time PCR,qPCR)技术在外周血白细胞中进行线粒体质量控制和氧化磷酸化相关基因表达量检测,并采集血生化、血糖等代谢指标,基因表达量、人口统计学信息的组间差异比较采用Mann-Whitney秩和检验或独立样本t检验,差异表达基因与临床代谢指标之间的相关分析采用Spearman相关分析。结果:患者组线粒体功能相关的关键基因NRF2、P62、MFN1、MFN2、YME1L、MF、MTATP8和AIF的基因表达量均显著低于对照组(FDR校正后P<0.05,检验值U=86、90、97、93、106、89、93、105,FDR均为0.038)。相关性分析显示,患者组MTATP8基因表达量与体重指数、总胆固醇水平、球蛋白水平呈负相关(r=-0.49、-0.58、-0.46,P=0.028、0.009、0.050),MFF基因表达量与球蛋白水平呈负相关(r=-0.48,P=0.040);对照组MFF基因表达量与腰围呈显著负相关(r=-0.53,P=0.020),AIF基因表达量与高密度脂蛋白胆固醇水平呈正相关(r=0.53,P=0.036)。结论:双相情感障碍患者线粒体质量控制和氧化磷酸化过程的多个关键基因表达量显著下调,差异表达基因与患者代谢异常显著相关,提示线粒体功能障碍可能与双相情感障碍患者代谢性疾病的高发相关。

Objective This study aims to explore the expression characteristics of mitochondrial function-related genes in patients with manic episodes of bipolar disorder and the correlation between differentially expressed genes and clinical metabolic indicators.Methods Twenty patients with manic episodes of bipolar disorder(patient group)and 20 healthy controls(control group)were included.Quantitative real-time PCR was used to detect mitochondrial quality control and oxidative phosphorylation-related gene expression in peripheral blood leukocytes,and several metabolic indicators were collected.Mann-Whitney test or independent sample t-test was used for comparison between groups.Spearman correlation test was used to analyze the correlation between gene expression and metabolic indicators.Results Mitochondria function-related genes,including NRF2,P62,MFN1,MFN2,YME1L,MFF,MTATP8,and AIF,were significantly lower in patients with bipolar disorder than in healthy controls(P<0.05,U=86,90,97,93,106,89,93,105,FDR=0.038).The expression level of MTATP8 was negatively correlated with BMI,total cholesterol,and globulin level in the patient group(r=-0.49,-0.58,-0.46,P=0.028,0.009,0.050).The expression level of MFF was significantly negatively correlated with waist circumference in healthy controls(r=-0.53,P=0.020)and with globulin level in the patient group(r=-0.48,P=0.040).The expression level of AIF was significantly and positively correlated with high-density lipoprotein cholesterol in healthy controls(r=0.53,P=0.036).Conclusion The expression of several genes involved in mitochondrial quality control and oxidative phosphorylation processes was significantly downregulated,and differentially expressed genes were significantly associated with metabolic index,suggesting that mitochondrial dysfunction may be related to the high risk of metabolic disease in patients with manic episodes of bipolar disorder.