谷胱甘肽S转移酶基因多态与皮质性年龄相关性白内障遗传易感性研究

发布时间：2018-04-18 03:21

本文选题：皮质性年龄相关性白内障 + GSTM1　；参考：《安徽医科大学》2014年博士论文

【摘要】：目的:谷胱甘肽S-转移酶(GSTs)是一组二聚体解毒酶。一般正常生理条件下,这种酶在氧化应激时,对机体的外源性和内源性有毒化合物发挥重要的解毒作用。最近的研究发现,GSTs基因多态与青光眼、年龄相关性黄斑变性以及白内障等多种眼部疾病相关。因此,本实验旨在探讨GSTs多态是否与中国汉族皮质性年龄相关性白内障相关。方法:收集中国汉族人皮质性年龄相关性白内障患者血标本422例和正常对照血标本312例,提取DNA标本,运用多重聚合酶联反应的方法对422例皮质性年龄相关性白内障患者和312例正常对照基因组中GSTM1和GSTT1基因多态位点进行基因分型。运用t检验比较患者组与正常人年龄之间是否有差异,运用卡方检验检测GSTM1和GSTT1在患者与正常组之间分布是否存在差异。收集患者的临床资料,生活环境等资料,进一步探讨皮质性年龄相关性白内障的危险因素。收集晶状体样本,提取蛋白质,用Elisa的方法检测不同条件的患者GSTM1蛋白的表达水平。结果:皮质性年龄相关性白内障患者GSTM1阳性的基因型频率显著高于正常对照(P=0.0002,OR 1.74,95%CI:1.30-2.34)。按照性别将患者分成两组,研究发现GSTM1(+)基因型与女性和男性的皮质性年龄相关性白内障患者显著相关(p=0.026,OR 1.58,95%CI:1.05-2.36;p=0.002,OR 1.97,95%CI:1.27-3.04)。GSTM1(+)GSTT1(-)基因型与白内障患者显著相关(p=0.002,OR 2.19,95%CI:1.33-3.60)。由于吸烟、强光照、饮酒等环境因素可能是皮质性年龄相关性白内障的危险因素,运用逻辑回归分析的方法发现强光照射和吸烟是皮质性年龄相关性白内障的发生的危险因素(分别是r=0.34,p=0.002;r=0.120,p=0.013)。GSTM1蛋白在皮质性ARC中表达量显著升高,尤其在强光照射和吸烟的ARC中显著增高。结论:GSTM1(+)的基因型和GSTM1(+)GSTT1(-)单倍体型与中国汉族人皮质性年龄相关性白内障的遗传易感性相关。在白内障的发病过程中,强光照射和吸烟可能是一个重要的危险因素。GSTM1基因多态可能通过调控改基因的表达来影响皮质性白内障的发生。
[Abstract]:Objective : Glutathione S - transferase ( GSTs ) is a kind of dimeric detoxification enzyme . In normal physiological condition , this enzyme plays an important role in detoxification of exogenous and endogenous toxic compounds in Chinese Han nationality . Patients were divided into two groups according to sex , and the study found that GSTM1 ( + ) genotypes were significantly correlated with women and men in cortical age - related cataract ( p = 0.026 , OR 1.58 , 95 % CI : 1.05 - 2.36 ; p = 0.002 , OR 1.97 , 95 % CI : 1.27 - 3.04 ) . GSTM1 ( + ) GSTT1 ( - ) genotype was significantly associated with cataract patients ( p = 0.002 , OR 2.19 , 95 % CI : 1.33 - 3.60 ) . Because smoking , intense illumination , alcohol consumption and other environmental factors may be a risk factor for cortical age - related cataract , the method of logistic regression analysis showed that strong light irradiation and smoking were the risk factors of cortical age - related cataract ( r = 0.34 , p = 0.002 ; r = 0.120 , p = 0 . 013 , respectively ) . Conclusion : GSTM1 ( + ) genotype and GSTM1 ( + ) GSTT1 ( - ) haplotype are associated with the genetic susceptibility of the Chinese Han nationality in the age - related cataract . In the pathogenesis of cataract , strong light irradiation and smoking may be an important risk factor . GSTM1 gene polymorphism may affect the occurrence of cortical cataract by regulating the expression of GSTM1 gene .

【学位授予单位】：安徽医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R776.1

【参考文献】