维生素D与原发性开角型青光眼发病的相关性研究

发布时间：2018-01-10 18:18

本文关键词：维生素D与原发性开角型青光眼发病的相关性研究　出处：《天津医科大学》2017年博士论文　论文类型：学位论文

【摘要】：目的:原发性开角型青光眼是眼压增高后损害视功能及视神经时,房角始终开放的一种神经退行性病变,病程缓慢但隐匿,具有遗传倾向,是一种多基因遗传病。流行病学研究显示高眼压、年龄、种族、家族史、糖尿病、近视、性别、白内障、偏头痛、外周血管痉挛、脑脊液压力变化、系统性高血压、血液流变学异常和遗传因素等是可能的危险因素。患者早、中期没有明显症状和/或典型的体征,晚期造成视功能及视神经不可逆的损害,目前治疗主要集中在控制眼压及视神经保护等方面。因此,应从遗传学角度在基因水平上探讨其发病机制,早期诊断及早期治疗,避免视神经损害的发生;易感基因及其多态性的研究应成为探讨发病机制的方向之一。患者机体维生素D营养状态及维生素D受体基因的某些多态性位点已被证明与糖尿病、高血压及近视等原发性开角型青光眼的危险因素相关。维生素D是否影响眼压存在争议。国外研究显示了1,25二羟基维生素D3能够调控动物的眼压,但机制不明。1,25二羟基维生素D3调控生理功能是受体依赖的。水通道蛋白1被检测到在小梁网等质膜中高表达,调控房水的分泌、外流及眼压。本研究探讨机体维生素D水平及维生素D受体基因多态性位点(Cdx-2、Fok I、Bsm I、Taq I、Apa I和Tru9 I)与原发性开角型青光眼是否存在相关联系;并在人小梁细胞水平观察1,25二羟基维生素D3对的水通道蛋白1及维生素D受体的作用。方法:1)应用酶联免疫吸附法检测原发性开角型青光眼病人血清1,25-二羟基维生素D3的含量,探讨原发性开角型青光眼与机体维生素D营养状态的相互关系。2)应用聚合酶链反应-限制性片段长度多态性分析技术和聚合酶链反应-高分辨溶解曲线分析技术及遗传学分析方法,检测原发性开角型青光眼病人维生素D受体基因的较常见的多态性位点(Cdx-2、Fok I、Bsm I、Taq I、Apa I和Tru9 I),并分析这些位点基因型和等位基因在体内的分布频率。3)应用蛋白质印迹法检测加入不同浓度梯度的1,25二羟基维生素D3前后,人小梁细胞AQP1及维生素D受体蛋白的表达。结果:1)71例原发性开角型青光眼患者血清中1,25二羟基维生素D3浓度为26.37 ng/ml±5.83 ng/ml,73例对照组血清1,25二羟基维生素D3浓度为30.43ng/ml±3.91 ng/ml。原发性开角型青光眼患者血清中1,25二羟基维生素D3水平明显低于对照组(p0.001)。2)Bsm I:原发性开角型青光眼组的Bb和bb基因型频率分别为25.35%和74.65%,对照组的Bb、bb基因型频率分别为5.48%和94.52%;基因型频率在原发性开角型青光眼组与对照组间比较经统计学分析结果有意义(p=0.001;χ2=10.982)。原发性开角型青光眼组和对照组B等位基因频率为12.68%和2.74%,等位基因频率在原发性开角型青光眼组与对照组间比较经统计学分析结果有意义(p=0.002;χ2=10.074;OR=5.153,95%CI:1.699~15.635)。Taq I:原发性开角型青光眼组的TT和Tt基因型频率分别为74.65%和23.35%,对照组的TT和Tt基因型频率分别为90.41%和9.59%,基因型频率在原发性开角型青光眼组与对照组间比较经统计学分析结果有意义(P=0.013;χ2=6.234)。原发性开角型青光眼组和对照组t等位基因频率为12.68%和4.79%,等位基因频率在原发性开角型青光眼组与对照组间比较经统计学分析结果有意义(p=0.018;χ2=5.641;OR=2.882,95%CI:1.165~7.132)。其余Cdx-2、Fok I、Apa I和Tru9 I位点多态性在原发性开角型青光眼组与对照组间的基因型及等位基因分布频率比较经统计学分析结果没有意义。3)1,25二羟基维生素D3能抑制人小梁细胞的水通道蛋白1表达,升高维生素D受体蛋白的表达。结论:1)体内较低水平的1,25二羟基维生素D3是原发性开角型青光眼患病的风险因素。2)限制性核酸内切酶Bsm I及Taq I两个位点与原发性开角型青光眼可能存在相关联系。Bsm I'B'和Taq I't'等位基因可能是保护基因。3)1,25二羟基维生素D3调控人小梁细胞的水通道蛋白1表达,维生素D受体也参与其中。
[Abstract]:Objective : To investigate the relationship between vitamin D level and vitamin D receptor gene polymorphism ( Cdx - 2 , Fok I , Bsm I , Taq I , Apa I and Tru9 I ) in patients with primary open angle glaucoma . Results : 1 ) The levels of 1 , 25 - dihydroxyvitamin D3 in serum of 71 patients with primary open angle glaucoma were 26.37 ng / ml 卤 5.83 ng / ml , respectively . Results : 1 ) The levels of 1 , 25 dihydroxyvitamin D3 in serum of 71 patients with primary open angle glaucoma were 26.37 ng / ml 卤 5.83 ng / ml . Results : 1 ) The frequencies of 1 , 25 dihydroxyvitamin D3 in serum of 71 patients with primary open angle glaucoma were 25.35 % and 74.65 % , respectively . The frequencies of genotype frequencies in primary open angle glaucoma group were 5.48 % and 94.52 % , respectively . The frequencies of genotype were significantly higher in primary open angle glaucoma group and control group ( p = 0.001 ; 蠂2 = 10.982 ) . The frequency of allele B allele was 12.68 % and 2.74 % in primary open angle glaucoma group and control group . The frequency of allele was statistically significant in primary open angle glaucoma group and control group ( p = 0.002 ; 蠂2 = 10.074 ; OR = 5.153 , 95 % CI : 1.699 ~ 15.635 ) . The frequencies of TT and TT genotype in primary open - angle glaucoma group were 74.65 % and 23.35 % , respectively , TT and TT genotype frequencies in control group were 90.41 % and 9.59 % , respectively , and genotype frequencies were statistically significant in primary open angle glaucoma group and control group ( P = 0 . 013 ; 蠂 2 = 6.234 ) . The frequency of t allele in primary open - angle glaucoma group and control group was 12.68 % and 4.79 % , and the frequency of allele was statistically significant in primary open - angle glaucoma group and control group ( p = 0 . 018 ; 蠂2 = 5.641 ; OR = 2.882 , 95 % CI : 1.165 ~ 7.132 ) . Conclusion : 1 . 25 - dihydroxyvitamin D3 is a risk factor for primary open - angle glaucoma . Conclusion : 1 ) Low level of 1 , 25 - dihydroxyvitamin D3 is a risk factor for primary open - angle glaucoma . Conclusion : 1 ) The restriction endonuclease Bsm I and Taq I ' t ' allele may be related to primary open - angle glaucoma .

【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R775

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