糖尿病视网膜病变基因多态性和遗传易感性

糖尿病视网膜病变（DR）是糖尿病严重的微血管并发症之一,其发生发展不仅与疾病的病程和血糖的控制情况有关,还表现出明显的家族聚集性和个体差异现象,这可能与遗传因素影响和遗传易感性的不同有关。DR是一个多基因作用的疾病,而每个基因存在不同的多态性。准确把握基因在DR发生发展过程中的作用机制及其表达的差异性,对今后早期诊断和防治DR的发生发展及提供新的诊疗手段具有重要意义。就有关DR相关基因的研究进展进行综述。     

糖尿病视网膜病变基因多态性研究现状

糖尿病视网膜病变(DR)是一种与血糖水平、病程长短以及遗传与环境因素相互作用所致的复杂疾病,其相关或易感基因的研究在近年来非常活跃.DR的相关候选基因包括醛糖还原酶基因、血管内皮生长因子基因、血管紧张素转换酶基因、一氧化氮合酶基因、非酶糖基化终末产物受体基因等.DR是多基因作用的疾病,而每个基因存在不同的多态性.准确把握基因在DR发生发展过程中的作用机制及其表达的差异性,对其早期诊断、防治DR的发生发展及开发新的诊疗手段具有重要意义.本文就有关DR相关基因的研究现状及进展进行综述.     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变（DR）是糖尿病最常见、最严重的并发症之一,发病率和致盲率逐年上升。通常认为其发生、发展与血糖控制情况、糖尿病病程长短等因素有关,而发病机制尚未完全明了。现在越来越多的证据表明其与遗传易感性不同有关。DR是一种多基因作用的疾病,近年来的研究已筛选出数十种可能与之相关的基因多态性,其中包括广受关注的血管内皮生长因子基因多态性、一氧化氮合酶基因多态性等。研究它们在DR发生发展过程中的作用机制,对今后DR风险预测、早期诊断及指导治疗具有重要意义。本文将对DR相关基因多态性的研究进展进行综述。     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变( diabetic retinopathy,DR)为糖尿病的严重并发症之一,是目前全球第二大致盲性疾病。早期的流行病学资料表明,其发生发展与血糖水平、糖尿病病程、血脂等多种因素相关。近年来,基因多态性与DR发生的相关性受到广泛关注。准确把握基因在DR发生发展过程中的作用机制及其表达的差异性,对DR早期诊断和防治具有重要意义。因此本文对DR发生有关的基因研究进展进行综述。     

糖尿病视网膜病变相关基因多态性的研究进展

糖尿病视网膜病变是重要致盲性眼病之一,其发生和进展与血糖水平、疾病病程、环境及遗传等多种因素有关。近年来,随着基因多态性与糖尿病视网膜病变关系的研究不断深入和扩展,已经筛选出可能与之相关的数十种基因现将与糖尿病视网膜病变密切相关基因的研究进展综述如下。     

糖尿病性视网膜病变基因多态性的研究进展

糖尿病性视网膜病变作为目前全球第二大致盲性疾病,是糖尿病最严重的并发症之一。寻找有效的预防和治疗方法,是目前急需解决的问题。有研究表明,糖尿病性视网膜病变的发病与遗传因素密切相关。本文主要对糖尿病性视网膜病变的相关基因的研究现状进行综述。     

一氧化氮及其合酶与糖尿病视网膜病变发病关系的研究进展

一氧化氮(nitric oxide,NO)是由一氧化氮合酶(nitric oxide synthase,NOS)催化合成的一种重要的信号分子和生物活性物质.目前的研究表明,NO及NOS在糖尿病视网膜病变(diabetic retinopathy,DR)的发生、发展中发挥重要的作用,因此NO及NOS成为当今治疗干预DR的一个研究热点,本文主要就NO及NOS与DR发病关系的研究进展作一综述.     

糖尿病视网膜病变黄斑囊样水肿与诱导型一氧化氮合成酶G-954C基因多态性

目的:分析中国人诱导型一氧化氮合成酶G-954C等位基因位点的基因表型在糖尿病视网膜病变黄斑囊样水肿患者与正常对照的差异。方法:病例对照,89例糖尿病视网膜病变黄斑囊样水肿的患者与年龄及性别匹配的90例健康对照纳入该项研究。研究采用了巢式聚合酶链式反应、限制性核酸内切酶技术、基因片段的序列测定。主要检测指标为诱导型一氧化氮合成酶G-954C位点的基因表型。结果:89例患者和90例健康对照的诱导型一氧化氮合成酶G-954C位点的基因表型全部检测结果为GG型。结论:诱导型一氧化氮合成酶G-954C位点的基因多态性可能在中国人为较低的变异频率,而且可能与糖尿病视网膜病变黄斑囊样水肿的易感性关系不大。     

VEGF基因多态性与糖尿病视网膜病变的关系

糖尿病视网膜病变（ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＤＲ）是多因素共同作用的复杂疾病,是糖尿病最严重的微血管并发症之一,其发生发展不仅与疾病本身及血糖的控制有关,还表现出明显的家族聚集现象和种族差异。目前,生长因子基因与ＤＲ相关性的研究是国内外的研究热点,但该类具有代表性的大样本量研究仍很缺乏,很多涉及与ＤＲ病理相关的候选基因中,血管内皮生长因子（ｖａｓｃｕｌａｒｅｎｄｏｔｈｅｌｉａｌｇｒｏｗｔｈｆａｃｔｏｒ,ＶＥＧＦ）基因在ＤＲ的早期预防、治疗以及延缓ＤＲ发生、发展中起着不可或缺的作用。准确把握ＶＥＧＦ基因多态性在ＤＲ发生发展过程中的作用,将对ＤＲ的早期防治具有重要的意义。本文就ＶＥＧＦ基因多态性与ＤＲ的相关性进行综述。     

内皮素、一氧化氮与糖尿病视网膜病变

内皮素和一氧化氮是两种作用相反的血管活性物质,两者共同作用影响眼底微循环血流动力学改变,与糖尿病视网膜病变中毛细血管的闭塞、内皮细胞的增殖、周细胞的凋亡以及基底膜的增厚密切相关,并对糖尿病视网膜病变的发病机制提出了新的认识,也为其治疗提供了新的思路。     

Association between sorbitol dehydrogenase gene polymorphisms and type 2 diabetic retinopathy

Diabetic retinopathy (DR) may affect 98% of diabetic patients, but its aetiology is poorly understood. Besides glycaemic exposure, genetic factors likely contribute to the onset of DR. The polyol pathway, including aldose reductase and sorbitol dehydrogenase (SDH), can be activated under hyperglycaemic conditions. In our work we searched for an association between the C-1214G and G-888C polymorphisms of the SDH gene promoter and the occurrence and progression of type 2 DR. Two hundred and fifteen unrelated individuals with type 2 diabetes mellitus (T2DM) were divided into three groups: without DR, with non-proliferative diabetic retinopathy (NPDR) and with proliferative diabetic retinopathy (PDR). Genotypes of the C-1214G (rs2055858) and G-888C (rs3759890) polymorphisms of the SDH gene were determined with DNA from the peripheral blood lymphocytes of patients by restriction fragment length polymorphism and allele-specific PCR, respectively. The genotype distributions were contrasted by the chi(2) test and the significance of the polymorphism was assessed by multiple logistic regression producing odds ratios (ORs) and 95% confidence intervals (CIs). We found an association (OR 1.73, 95% CI 1.06-2.83) between NPDR and the G allele of the G-888C polymorphism. There was no association between NPDR and the other polymorphisms of the SDH gene. No differences were found in the distributions of these polymorphisms between patients with PDR and those with NPDR. A weak association (OR 2.0, 95% CI 1.29-3.07) was found between DR and the G allele of the G-888C polymorphism. Analysis of the combined genotypes (haplotypes) of both polymorphisms revealed associations between the C/G-C/G genotype and NPDR (OR 2.95, 95% CI 1.07-8.13) as well as DR in general (OR 2.91, 95% CI 1.15-7.36). The G-888C polymorphism of the SDH gene may be associated with the onset of DR rather than with its progression, and its effect may be strengthened by the interaction with the C-1214G polymorphism, but this association is rather weak and requires further study.     

巨细胞病毒与2型糖尿病视网膜病变关系的临床研究

目的:探讨巨细胞病毒(cytomegalovirus,CMV)感染与2型糖尿病视网膜病变(diabetic retinopathy,DR)的关系。方法:采用聚合酶链反应(chain reaction technique,PCR)技术分别检测T2DM患者86例(单纯T2DM组40例、视网膜病变组46例)以及正常对照组30例外周血中的CMV-DNA,测定血浆内皮素(endothelin,ET)和一氧化氮(nitricox-ide,NO)。结果:T2DM视网膜病变组CMV-DNA检测阳性率(65.2%)明显高于单纯T2DM组(35.0%)和对照组(13.3%,P<0.01),T2DM视网膜病变组ET、NO含量与单纯T2DM组和对照组比较也有显著差异。结论:CMV感染与糖尿病视网膜病变的发生发展有关,CMV感染可能加重糖尿病视网膜病变。     

川芎嗪联合氨基胍对糖尿病大鼠视网膜保护作用的机制

目的　探讨川芎嗪联合氨基胍对糖尿病视网膜病变防治作用及其机制。方法　用链尿佐菌素 (STZ)制作糖尿病大鼠动物模型 ,分为正常对照组、糖尿病对照组、糖尿病氨基胍治疗组、糖尿病川芎嗪 +氨基胍治疗组 ,于第 12周测定大鼠视网膜组织NO的含量、NOS活性和AR的活性。结果　糖尿病川芎嗪 +氨基胍治疗组、糖尿病氨基胍治疗组大鼠视网膜组织NOS及AR活性显著低于糖尿病对照组 (P <0 0 1) ,NO的含量升高 (P <0 0 1) ;糖尿病氨基胍治疗组仍高于正常对照组 (P <0 0 1) ,NO的含量降低 (P <0 0 1) ;糖尿病川芎嗪 +氨基胍治疗组与正常组无显著差异。结论　川芎嗪联合氨基胍能够抑制糖尿病大鼠视网膜组织NOS、AR活性 ,从而对糖尿病视网膜病变起一定保护作用     

Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population

AIM: To assess if the included vascular endothelial growth factor (VEGF) polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus (T2DM). METHODS: A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study (ETDRS) standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts. RESULTS: In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR (95% CI)=0.44(0.08-2.2); P=0.25] and rs2010963 [OR (95% CI)=0.63(0.25-1.6); P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows: rs3025021 vs rs3025035: D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963: D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963: D’=0.505, r2=0.0214, P=0.142. CONCLUSION: This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.     

一氧化氮合酶基因多态性与糖尿病视网膜病变相关性研究

目的　观察中国汉族人群中血管内皮原生型一氧化氮合酶(ecNOS)基因的多态性与糖尿病视网膜病变（DR）之间的相关性。方法　166例临床确诊为非胰岛素依赖型糖尿病患者为病例组,选取无糖尿病、高血压、肾病,年龄40岁以上,个体间无血缘关系的85例白内障、骨折患者和健康体检者为正常对照组。病例组患者根据有无视网膜病变和荧光素眼底血管造影检查结果分为无DR组、非增生期DR组（BDR组）和增生期DR组（PDR组）。病例组和正常对照组受检者均为汉族。抽取外周静脉血,提取DNA,采用聚合酶链反应（PCR）检测ecNOS基因第四内含子中27个碱基对（bp）重复的多态性。结果 PCR产物测序结果经检索GeneBank,扩增序列与GeneBank中ecNOS基因相应区域的序列相一致,显示在汉族人群中同样存在27个bp的重复序列,等位基因b重复5次,等位基因a重复4次。PCR检测结果显示,在正常对照组和无DR组、BDR组、PDR组中均存在2种等位基因和3种基因型。正常对照组中基因型bb、ab、aa分别为80.0％、16.5%、3.5％、无DR组分别为77.2％、13.9%、8.9％、BDR组分别为80.5％、17.1%、2.4％、PDR组分别为78.3％、13%、8.7％;正常对照组、无DR组、BDR组、PDR组两两比较,等位基因频率（χ²=1.841）和基因型频率（χ²=3.847）均无统计学意义（P＞0.5）。Logistic回归分析结果也显示DR与ecNOS基因重复多态性无关。结论　中国汉族人群ecNOS基因第四内含子存在27个bp重复的多态性,但可能与非胰岛素依赖型糖尿病患者视网膜病变无关。      

MMP-2 gene polymorphisms in type 2 diabetes mellitus diabetic retinopathy

AIM: To study the association between polymorphisms of the MMP-2 gene and diabetic retinopathy (DR). METHODS:MMP-2 C-1306T and C-735T SNPs was genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis in 151 DR patients and 150 healthy individuals served as control. RESULTS: There is no significant difference between the patient and control groups in allele or genotype distributions of MMP-2 C-735T (P=0.263 and P=0.248). Also, there is no significant difference between the patient and control in allele of MMP-2 C-1306T (P=0.03). However the result has significant deviation of C/C, C/T, T/T genotypic frequencies between the patient and control groups in MMP-2 C-1306T (P=0.008). We found that subjects with the MMP-2 C-1306T genotype had an overall 2-fold increase in the risk of developing DR [adjusted odds ratio (OR)=2.446; 95% confidence interval (CI)=1.239-4.829] compared with those with the T-1306T or C-1306T genotype. Stratification analysis showed that the MMP-2 -1306C/T and -735C/T SNPs are not associated with the development of NPDR to PDR of DR in North Chinese Han population. CONCLUSION: MMP-2 C-1306T genotypes may be associated with DR development in the Chinese population. However, there is no relationship between the MMP-2 C-735T genotypes with the development of DR.