视网膜视杆细胞盘膜边缘蛋白在视网膜色素变性发病机制中作用的研究  

Role of retinal rod cell disc marginal protein in the pathogenesis of retinitis pigmentosa

作　　者：于永斌[1] 马瑛娜[1] 初海迪[1] 高维奇[1] 刘平[1] 崔浩[1] YU Yong-bin;MA Ying-na;CHU Hai-di;GAO Wei-qi;LIU Ping;CUI Hao(Eye Hospital,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第一医院眼科医院

出　　处：《哈尔滨医科大学学报》2019年第4期385-392,共8页Journal of Harbin Medical University

基　　金：黑龙江省教育厅海外学人科研资助项目(1055HQ014)

摘　　要：目的研究peripherin基因的突变与RP发病的关系。方法收集6例汉族视网膜色素变性患者和4例正常健康对照者12 mL外周血样本,进行全外显子测序分析。在大量原始数据的基础上,进行深度分析及基因热图分析。进一步进行peripherin基因GO分析,解读peripherin基因的功能。收集235例汉族视网膜色素变性患者和248例正常健康对照者12 mL外周血样本,质谱分析peripherin基因rs62645931,rs61755792,rs7764439,rs425876与RP发病的关系。Swissmodel软件建立SNP位点改变前后peripherin基因编码蛋白3D模型,了解SNP位点突变对蛋白的影响,定点到蛋白的功能。结果在全外显子测序分析6例汉族视网膜色素变性患者基因组得到大量原始数据后,进一步进行深度基因分析及基因热图分析,发现peripherin基因在病例样本中高表达。peripherin基因GO分析表明peripherin基因与细胞黏附有关;与细胞表面受体信号通路有关;与视觉感知及视网膜发育有关。质谱分析发现在235例RP患者中,rs61755792是与正常对照人群相比,有统计学意义的突变位点。SWISS-Model软件对peripherin基因在编码区发生了Arg-172-Trp(CGG→GGG)的错义突变所引起的蛋白三维结构的改变进行分析,发现peripherin基因编码区原Arg氨基酸所在的区域有碳原子构成的共价键有类似受体的结构。当CGG→GGG发生后,原Arg成为了Trp,可以看到Arg氨基酸所在的区域碳原子的数量增多,并且与原来相比,长链的共价键变成了闭合环状的共价键。结论在中国东北汉族人群中,peripherin基因单核苷酸多态性rs61755792位点与RP的发病有关。Objective To explore the relationship between the mutation of peripherin gene and the pathogenesis of RP. Methods 12 mL peripheral blood samples from 6 Han patients with retinitis pigmentosa and 4 healthy controls were collected and sequenced. On the basis of a large number of original data, in-depth analysis and gene thermogram analysis were carried out. GO analysis of peripherin gene was carried out to understand the function of peripherin gene. 12 mL peripheral blood samples were collected from 235 patients with retinitis pigmentosa and 248 healthy controls. The relationship between peripherin gene rs62645931, rs61755792, rs7764439, rs425876 and RP was analyzed by mass spectrometry. Swissmodel software established a three-dimensional model of peripherin gene-encoded protein before and after SNP locus change, to understand the effect of SNP locus mutation on protein, and to locate the function of protein. Results After a large number of original data were obtained from genome sequencing of 6 Han patients with retinitis pigmentosa, further in-depth gene analysis and gene thermogram analysis showed that peripherin gene was highly expressed in the case samples. GO analysis of peripherin gene showed that peripherin gene was related to cell adhesion, cell surface receptor signaling pathway, visual perception and retinal development. Mass spectrometry analysis revealed that rs61755792 was a significant mutation site in 235 RP patients compared with the normal control group. SWISS-Model software was used to analyze the changes of three-dimensional structure of peripherin protein caused by the missense mutation of Arg-172-Trp(CGG→GGG) in the coding region of peripherin gene. It was found that the covalent bonds of carbon atoms in the original Arg amino acid region of peripherin gene coding region had receptor-like structures. When CGG→ GGG occurs, the original Arg becomes Trp. It was seen that the number of carbon atoms in the region where Arg amino acids reside increased, and compared with the original, the long c

关 键 词：视网膜色素变性 peripherin基因 基因多态性 眼 

分 类 号：R774.13[医药卫生—眼科]