正常眼压性青光眼患者线粒体相关基因组变异研究

Investigation of mitochondria-related genome in normal tension glaucoma patients

目的探索线粒体相关基因组的变异是否与正常眼压性青光眼(NTG)相关。方法抽取NTG患者、高眼压性原发性开角型青光眼(HTG)患者和年龄相关性白内障(ARC)患者的外周静脉血样本各10例,提取基因组DNA并构建测序文库。使用靶向二代测序技术检测线粒体相关基因组的变异并进行组间比较。结果与ARC组相比,NTG组在12S rRNA基因(P=0.009)与rRNA编码区(P=0.009)的罕见变异更少。各组的线粒体单倍型分布差异无统计学意义(P=0.366)。在线粒体相关核基因组,与ARC组相比,NTG组含有更多的缺失(P=0.006)和罕见的移码突变(P=0.002);与HTG组相比,NTG组的总突变数(P=0.005)和罕见突变数(P=0.002)更多,且罕见突变数占总突变数比值更大(P=0.005)。结论线粒体相关基因组的变异可能是NTG的危险或保护性因素。

Objective To determine whether mitochondria-related genome variants are associated with normal tension glaucoma(NTG).Methods Peripheral blood samples from 10 NTG patients,10 high tension primary open angle glaucoma(HTG)patients and 10 age-related cataract(ARC)patients were obtained.Variations of mitochondria-related genome were detected by next generation sequencing(NGS)and compared among the three groups.Results NTG group contained fewer rare variants in 12S rRNA gene(P=0.009)as well as in rRNA coding regions(P=0.009)compared to ARC group.The distribution of mitochondrial haplotype was balanced among the three groups(P=0.366).In mitochondria-related nuclear genome,NTG group contained more deletions(P=0.006)and rare frameshifts(P=0.002)than ARC group.NTG patients also harbored more total variants(P=0.005)and rare variants(P=0.002)with a larger rare variants/total variants ratio(P=0.005)than HTG patients.Conclusions Our results indicated that variants in mitochondria-related genome might exert either protective or promotive effects on the pathogenesis of NTG.