单体型B与携带线粒体m.1555A>G突变耳聋相关性研究  

Study on the correlation between haplotype B and deaf family with mitochondrial m.1555A>G mutation

作　　者：卫梦倩 金聪囡 徐轩昂 郑斌娇[1,2] Wei Mengqian;Jin Congnan;Xu Xuan’ang;Zheng Binjiao(School of Laboratory Medicine and Life Science,Wenzhou Medical University,Wenzhou 325035,China;Attardi Institute of Mitochondrial Biomedicine,Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]温州医科大学检验医学院生命科学学院,温州325035 [2]温州医科大学Attardi线粒体生物医学研究院,温州325035

出　　处：《国际遗传学杂志》2022年第3期164-168,共5页International Journal of Genetics

基　　金：温州市医疗卫生项目(Y20190081)。

摘　　要：目的探究单体型B与线粒体m.1555A>G突变致聋的相关性。方法采集单体型为B且携带m.1555A>G家系(TP023)成员外周血,建立永生化淋巴细胞系作为实验组(D组);选取单体型非B但携带m.1555A>G的永生化淋巴细胞(S组)和单体型为B但不携带m.1555A>G的永生化淋巴细胞(C组)为对照组;分别对三组细胞的线粒体膜电位(mitochondrial membrane potential,MMP)、线粒体蛋白表达、细胞活性氧(reactive oxygen species,ROS)、三磷酸腺苷(adenosine triphosphate,ATP)水平进行检测,评估线粒体功能。结果相比于C组,D组细胞的MMP下降29.5%(P<0.001),ROS水平上升30.8%(P<0.001),ATP产量下降39.0%(P<0.001),S组细胞MMP下降21.3%(P=0.002),ROS水平上升8.7%(P=0.202),ATP产量下降11.2%(P=0.661);两组细胞的ND4、CytB等蛋白表达均有不同程度的下降。结论线粒体单体型B可能是导致m.1555A>G突变携带者的耳聋外显率增高的原因。Objective To investigate the effect of mitochondrial haplotype B on cell function of m.1555A>G mutation.Methods A family with mitochondrial haplotype B and m.1555A>G was used as the object,with mitochondrial haplotype B not with m.1555A>G,without mitochondrial haplotype B but with m.1555A>G were used as controls;Peripheral blood was collected to construct an immortality lymphocyte line.Mitochondrial function was evaluated in mitochondrial membrane potential(MMP)level,reactive oxygen species(ROS),adenosine triphosphate(ATP)synthesis level,and protein synthesis level.Results Cell function assay showed that,comparing with group C,group D is decreased by 29.5%(P<0.001)on MMP level,by 30.8%(P<0.001)on ROS level,by 39.0%(P<0.001)on ATP production.Group S is decreased by 21.3%(P=0.002)on MMP level,by 8.7%(P=0.202)on ROS level,by 11.2%(P=0.661)on ATP production.ND4 and CytB were decreased to varying degrees in both groups,and the expression of experiment group in the former group was more obvious.Conclusion Mitochondrial haplotype B and m.1555A>G mutant cells have severe functional damage.Mitochondrial haplotype B may affect the deafness phenotype expression which with m.1555A>G mutant.

关 键 词：线粒体单体型B 线粒体基因突变 遗传性耳聋 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]