海南黎族2型糖尿病患者VEGF基因多态性与糖尿病视网膜病变关系

目的:探讨海南黎族2型糖尿病患者血管内皮细胞生长因子(VEGF)基因rs2010963和rs3025039的单核苷酸多态性与糖尿病视网膜病变(DR)的相关性。方法:前瞻性研究。随机收集2016-09/2019-10海南黎族2型糖尿病患者89例,其中非增殖期DR(NPDR)患者30例、增殖期DR(PDR)患者33例,2型糖尿病无视网膜病变(DWR)患者26例作为对照。运用聚合酶链式反应-限制性片段长度多态性技术测序法,进行VEGF基因相应位点的多态性分析,比较基因型和等位基因频率的差别。结果:在rs2010963位点上,与DWR组比较,PDR组CC基因型显著升高(P<0.016667),PDR组CG基因型显著降低(P<0.016667),三组患者的GG基因型和C、G等位基因分布比较均无差异(P>0.05)。在rs3025039位点上,DWR组,NPDR和PDR组三组的CC、CT基因型及C、T等位基因分布均无差异(均P>0.05)。海南黎族PDR患者尿素、肌酐水平较DWR和NPDR组均显著升高(均P<0.05)。结论:海南黎族2型糖尿病患者VEGF基因rs2010963基因多态性与DR发生有关,CC基因型可能是DR发生的遗传危险因素,增加PDR的易感性。rs2010963基因多态性对于PDR具有协同作用。     

中国人VEGF基因多态性与DR的关系

目的:探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)I/D基因多态性与糖尿病视网膜病变(diabetic retinopathy,DR)的关系。方法:应用PCR-RFLP方法检测91例2型糖尿病患者和30例对照者的VEGF I/D基因和VEGF水平。结果:NPDR组和PDR组DD基因型频率显著高于NDR组和对照组(P<0.01);NPDR组和PDR组血清VEGF水平显著高于NDR组和对照组(P<0.01)。结论:VEGF I/D基因多态性很可能与DR的发生发展有关,D等位基因可能是DR的易感基因。     

Nrf2基因多态性与糖尿病视网膜病变的相关性研究

目的：探讨陕西地区汉族人群中,核因子E2相关因子2(Nrf2)基因多态性与糖尿病视网膜病变(DR)的相关性。

方法：收集2016-01/2017-01在我院治疗的386例2型糖尿病(T2DM)患者分为无视网膜病变(DWR)组181例,增生期DR(PDR)组62例和非增生期DR(NPDR)组143例。另外,收集120例非糖尿病且无视网膜疾病的患者作为对照组。采用聚合酶链反应(PCR)联合DNA直接测序法检测Nrf2基因启动子rs6721961位点单核苷酸多态性。

结果： DWR组与对照组比较,rs6721961位点基因型和等位基因分布频率均无差异(P>0.05); PDR组和NPDR组分别与对照组和DWR组比较,突变纯合子(AA基因型)和突变基因(A等位基因)分布频率差异均有统计学意义(P<0.05)。PDR组和NPDR组比较,基因型和等位基因分布频率均无差异(P>0.05)。Logistic多因素回归分析结果显示rs6721961位点A等位基因与DR发生相关(OR=1.532, 95%CI ：1.169～2.008, P=0.014)。

结论： Nrf2基因多态性可能与DR遗传易感性相关。     

Association of vascular endothelial growth factor -634G/C and receptor for advanced glycation end products G82S gene polymorphisms with diabetic retinopathy

AIM: To investigate the association of receptor for advanced glycation end products (RAGE) G82S and vascular endothelial growth factor (VEGF) -634 G/C gene polymorphisms with diabetic retinopathy (DR). METHODS: Our cross-sectional study included 61 diabetic patients, 12 of them had proliferative diabetic retinopathy (PDR), 15 had non proliferative diabetic retinopathy (NPDR), 34 had no diabetic retinopathy (NDR) and 61 healthy controls. Participants were tested for RAGE G82S and VEGF -634 G/C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found a significant association between VEGF -634 G/C polymorphism and PDR as PDR patients had increased incidence of VEGF -634 CC genotype compared to NDR patients [odds ratio for CC vs (GC+GG)=6.5, 95% CI=1.5-27.8, P=0.021]. Also VEGF -634 CC genotype and C allele were significantly higher in the PDR than in NPDR patients, which is a novel finding in our study (P=0.024, 0.009 respectively). The mean triglycerides level was significantly higher in diabetic patients with CC genotype (P=0.01) as compared to patients with other genotypes. All cases and control subjects were of the same heterozygous RAGE 82G/S genotype. CONCLUSION: Patients carrying VEGF -634 C polymorphism have a higher risk of PDR development, so VEGF -634 G/C polymorphism could be used as a predictive marker for PDR in diabetic patients. We could not find a significant association between RAGE G82S polymorphism and DR.     

糖尿病视网膜病变患者血清VEGF、ES、TKLK、TSP、sICAM-1水平的变化及意义

目的:探讨血清血管内皮细胞生长因子(VEGF)、内皮抑素(ES)、血小板反应蛋白(TSP)、组织激肽释放酶(TKLK)及可溶性细胞间黏附分子-1(sICAM-1)水平在糖尿病视网膜病变(DR)患者血清中的变化及其临床意义.方法:选取我院2014-01/2016-12收集的无眼底病变的糖尿病患者60例(DM组)、非增殖性糖尿病视网膜病变患者60例(NPDR组)、增殖性糖尿病视网膜病变患者60例(PDR组)和同期健康体检对象60例(对照组),检测四组患者血清VEGF、ES、TSP、TKLK、sICAM-1水平并进行比较分析.结果:PDR组患者的血清VEGF、TKLK、sICAM-1水平均显著高于NPDR组、DM组、对照组(P<0.05);PDR组患者的血清ES水平均显著低于NPDR组、DM组、对照组(P<0.05).NPDR组患者的血清VEGF、TKLK、ES水平均显著高于DM组和对照组(P<0.05).NPDR组患者的血清VEGF与ES、TKLK、sICAM-1水平均呈显著的正相关关系(P<0.05).PDR组患者的血清VEGF与TKLK、sICAM-1水平均呈显著的正相关关系(P<0.05),PDR组患者的血清VEGF与ES、TSP相关性不显著(P>0.05).结论:DR患者血清ES、TSP、TKLK、sICAM-1水平均发生显著改变,通过调节VEGF水平影响DR进程.     

Impact of variants in the VEGF gene on progression of proliferative diabetic retinopathy

Background  The development of diabetic retinopathy is associated with the duration of diabetes and HbA1c levels. However, the familial aggregation of diabetic retinopathy is consistent with genetic susceptibility. Recently, a –634C/G polymorphism in the vascular endothelial growth factor (VEGF) gene was shown to be associated with diabetic retinopathy. To clarify the contribution of the VEGF gene in the development of diabetic retinopathy we analyzed variants in this gene among 469 Japanese patients with type 2 diabetes. Methods  DNA from each patient was typed for –634C/G and –2578C/A polymorphisms using conventional polymerase chain reaction techniques. The vitreous fluid samples were obtained from 40 patients with PDR for measurement of VEGF levels. Results  We found a significantly higher frequency of the A allele in the group with proliferative diabetic retinopathy (PDR) than in the control group at –2578C/A polymorphism (p = 0.036). Moreover, if the subjects were grouped according to the duration of diabetes and status of diabetic retinopathy (a first group consisting of subjects with longer duration (>20 y) of diabetes without any retinopathy (n = 102), and a second group of those with shorter diabetes (<15 y) but having retinopathy (n = 35), the genotype distribution at -2578 C/A polymorphism was again significantly higher in the second group (p = 0.005) and differed significantly (p = 0.002) in a recessive model. The risk of the AA for PDR was 7.7 (95%, CI: 1.8–30.9). Conclusions  The AA genotype at –2578C/A polymorphism in the VEGF gene is associated with proliferative diabetic retinopathy. No significant association with –634 C/G polymorphism was confirmed. There is no potential conflict of interest and no involvement of funding sources in this research.     

VEGF和bFGF在蒙古族糖尿病视网膜病变中的表达

目的：研究血管内皮生长因子( vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)在蒙古族糖尿病患者视网膜病变中的表达,探讨其中在糖尿病视网膜病变(diabetic retinopathy, DR)发生过程中的作用。
　　方法：对2013-02/2015-02在内蒙古自治区人民医院眼科83例蒙古族糖尿病患者根据视网膜病变情况分为：无糖尿病视网膜病变患者(NDR 组)25例、背景型糖尿病视网膜病变患者(NPDR 组)31例、增殖型糖尿病视网膜病变患者(PDR 组)27例。36例年龄匹配健康志愿者作为对照组。分别采集患者外周静脉血,采用 ELISA 法分别对血清中 VEGF 和 bFGF 的表达情况进行测定。
　　结果：蒙古族糖尿病患者血清中 VEGF 和 bFGF 的水平显著高于对照组;三组蒙古族糖尿病患者中,PDR 患者血清VEGF 和 bFGF 水平高于 NDR 和 NPDR 组,差异具有统计学意义(P<0.05),NPDR 患者血清 VEGF 和 bFGF 水平又显著高于 NDR(P<0.05)。
　　结论：高表达的 VEGF 和 bFGF 可能是蒙古族 DR 发生、发展的重要致病因素。     

不同程度糖尿病性视网膜病变患者中央角膜厚度的分析

目的：研究不同程度糖尿病性视网膜病变（DR）患者中央角膜厚度（CCT）的变化及相关性。方法：采用角膜内皮显微镜对 65例130眼不同程度糖尿病性视网膜病变患者（均为2型糖尿病患者）及年龄、性别相匹配的35例70眼正常健康人进行中央角膜厚度检测,并对结果进行统计分析。结果：轻度、中度非增生期糖尿病视网膜病变（NPDR）组与对照组比较,中央角膜厚度差异无统计学意义（P〉0.05）,而重度NPDR组和增生期糖尿病视网膜病变（PDR）组的CCT较对照组增厚,差异有统计学意义（P〈0.05）; 组间比较中：轻度NPDR组与重度NPDR组和PDR组比较,差异有统计学意义（P〈0.05）,中度NPDR组与PDR组比较,差异有统计学意义（P〈0.05）; 且CCT随DR的程度加重而增厚,呈正相关（r=0.173,P〈0.05）。结论：糖尿病性视网膜病变的中央角膜厚度随着病变加重逐渐增厚。DR患者治疗过程中,尤其是内眼手术时应特别注意保护角膜内皮,减少并发症的发生。     

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.     

An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy

Background Diabetic retinopathy is a highly prevalent cause of visual loss in Western countries. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in the development of the proliferative stage of this disease. Reports have suggested that polymorphisms at positions-460 and -634 of the 5′ untranslated region of the VEGF gene increase its basal promoter activity. Methods To investigate whether polymorphisms are associated with diabetic retinopathy, 215 patients with type 2 diabetes mellitus (T2DM) were enrolled. Among them, 82 subjects had proliferative diabetic retinopathy (PDR), 72 had non-proliferative diabetic retinopathy (NPDR), and 61 individuals without retinopathy served as controls. Two polymorphisms of the VEGF gene, a G→C transversion at-634 (the G/C polymorphism) and a C→T transition at-460 (the C/T polymorphism), were investigated by restriction fragment length polymorphism PCR and allele-specific PCR respectively. Results We did not find any association between the C/T polymorphism and diabetic retinopathy. However, the G/C polymorphism genotype distribution and the frequency of the C allele were significantly higher in the NPDR group than in control patients (OR = 1.69, 95% CI = 1.03–2.79). Analysis of the distribution of combined genotypes of the VEGF gene revealed the prevalence of the C/C-C/C genotype in NPDR patients (OR = 8.26, 95% CI = 1.79–37.99) and C/G-CC in PDR patients (OR = 3.36, 95% CI = 1.39–8.12). Conclusions Occurrence of the -634C allele appears to be associated with increased VEGF gene promoter activity, and the G/C polymorphism might serve as a predictive factor for the development of diabetic retinopathy. The authors have no financial or other interest in any products used or described in this study. This work was supported by a statutory grant of the Medical University of Warsaw, Warsaw, Poland, and grant 505/363 from the University of Lodz (JB).     

Dickkopf-3蛋白在糖尿病视网膜病变患者血浆中的表达

目的：观察 Dickkopf-3在糖尿病视网膜病变( diabetic retinopathy,DR)患者循环血中的表达水平,研究Dickkopf-3在糖尿病视网膜病变发生发展中的变化,探讨其在糖尿病视网膜病变早期诊断中的意义。
　　方法：选择2型糖尿病患者85例,其中非增殖期糖尿病视网膜病变( non-proliferative DR,NPDR)患者23例、增殖期糖尿病视网膜病变( proliferative DR,PDR)患者30例及无视网膜病变( non-diabetic retinopathy,NDR)患者32例。选择同期健康体检者为对照组(80例)。收集血清样本,采用酶联免疫吸附法( ELISA )双抗体夹心法检测循环血中Dickkopf-3的相对表达水平,并比较各组血浆Dickkopf-3的水平。
　　结果：糖尿病视网膜病变患者血浆Dickkopf-3平均含量为430.16±198.11pg/mL,明显低于健康对照组(627.48±294.45pg/mL)及无视网膜病变患者(601.99±194.16pg/mL),差异有统计学意义(P<0.05);而无视网膜病变与健康对照组Dickkopf-3水平比较,差异无统计学意义( P=0.729);增殖期糖尿病视网膜病变患者Dickkopf-3的水平(396.38±185.59pg/mL)低于非增殖期糖尿病视网膜病变患者(538.82±187.20pg/mL),差异有统计学意义(P=0.002)。
　　结论：Dickkopf-3蛋白水平降低可能与糖尿病视网膜病变的发生发展有关,与增殖期糖尿病视网膜病变有显著相关性。循环血中Dickkopf-3蛋白对糖尿病视网膜病变具备一定的鉴别效能,有可能成为糖尿病视网膜病变患者外周血的检测指标。     

糖尿病视网膜病变严重程度与角膜上皮基底神经丛变化间的相关性

目的：探讨糖尿病视网膜病变(DR)严重程度与角膜上皮基底神经丛(SNP)变化间的相关性。

方法：研究纳入我院2018-01/2021-05收治2型糖尿病(T2DM)患者132例132眼和年龄相关性白内障患者80例80眼,其中T2DM患者中包括非DR(NDR)患者52例52眼,非增生性DR(NPDR)患者40例40眼及增生性DR(PDR)患者40例40眼,分析一般资料和角膜激光扫描共焦显微镜检查资料,采用Spearman秩相关分析评价DR临床分期与神经纤维长度间相关性。

结果：四组性别和年龄比较均无差异(P>0.05); PDR组糖尿病病程显著长于NPDR组、NDR组(P<0.05); NPDR组糖尿病病程显著长于NDR组(P<0.05); 年龄相关性白内障组空腹血糖和糖化血红蛋白水平均显著低于其他三组(P<0.05); PDR组最佳矫正视力显著低于NPDR组、NDR组(均P<0.05); NPDR组最佳矫正视力显著低于NDR组(P<0.05); 年龄相关性白内障组神经纤维长度值均显著大于NDR组、NPDR组及PDR组(P<0.05); PDR组神经纤维长度值显著小于NPDR组(P<0.05); Spearman秩相关分析结果显示,DR分期与神经纤维长度间呈负相关(r_s=-0.347,P<0.001)。

结论：DR病情严重程度与角膜上皮基底神经丛变化间具有相关性,PDR患者神经纤维长度较NPDR显著缩短; PDR和NPDR均存在神经结构缺失,T2DM眼底病变治疗时注意对眼表病变情况评估及处理。     

糖尿病黄斑水肿对抗VEGF药物治疗的不同反应与糖尿病视网膜病变程度的相关性

目的：通过观察糖尿病黄斑水肿(diabetic macular edema,DME)患者对于玻璃体腔注射抗VEGF治疗的不同反应和糖尿病视网膜病变(diabetic retinopathy,DR)的不同程度之间的相关性,进一步阐释糖尿病黄伴水肿的发病机制和治疗策略。

方法：选择非增生性糖尿病视网膜病变(non proliferative diabetic retinopathy,NPDR)伴发DME的患者27例33眼,增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)伴发DME的患者32例34眼。均给予玻璃体腔注射抗VEGF药雷珠单抗,观察两组患者对该药的不同反应,并进行统计学比较。

结果：分别把患者治疗3、6mo时的最佳矫正视力(best corrected visual acuity,BCVA)和黄斑中心视网膜厚度(central macular thickness,CMT)和治疗前的BCVA、CMT作比较,NPDR组有统计学差异(P<0.05),PDR组无统计学差异(P>0.05)。NPDR组和PDR组比较,3、6mo时的BCVR和CMT均有统计学差异(P<0.05)。

结论：糖尿病视网膜病变的不同程度影响着糖尿病黄斑水肿对抗VEGF治疗的反应。     

miR-132在糖尿病视网膜病变患者血浆中的表达及其临床意义

目的：分析miR-132在糖尿病视网膜病变(DR)患者血浆中的表达及与DR的关系。

方法：前瞻性研究,选取2015-07/10于我院确诊的55例糖尿病患者,按DR国际临床分期标准将患者分为5组。背景期：无明显视网膜病变组13例(A组); 非增殖期(NPDR)33例,包括：轻度NPDR组10例(B组),中度NPDR组11例(C组),重度NPDR组12例(D组); 增殖期(PDR)9例(E组)。另选取我院体检健康者12例作为健康对照组(F组)。应用实时荧光定量PCR(qRT-PCR)技术检测不同分期DR患者外周血浆中miR-132的相对表达量,并比较各组间差异。

结果：除无明显视网膜病变组外,其余各组DR患者与健康对照组相比,血浆中miR-132的表达水平均明显下降(P<0.05); 非增殖期组间、非增殖期与增殖期组间比较,miR-132表达量无差异(P>0.05)。

结论：miR-132在NPDR和PDR患者血浆内低表达,可能成为DR治疗的生物标志物。     

OCTA在DR患者黄斑血流密度观察中的应用

目的:应用光学相干断层扫描血管成像技术(optical coherence tomography angiography,OCTA)观察糖尿病视网膜病变(diabetic retinopathy,DR)患者黄斑血流密度的改变和临床意义.方法:收集28例47眼DR患者纳入研究组(DR组),依据DR国际临床分期标准将DR患眼分为两组,其中非增殖组(NPDR组)19例30眼和增殖组(PDR组)11例17眼.取年龄相匹配的27例46眼健康眼作为对照组.所有入选受试者均应用OCTA对黄斑区视网膜行3mm×3mm范围模式扫描,获得4个层面黄斑血流密度图,同时测量3个层面黄斑血流密度,包括表层视网膜层、深层视网膜层和脉络膜毛细血管层.结果:DR组表层视网膜、深层视网膜及脉络膜层毛细血管层黄斑血流密度分别为0.4963±0.0840、0.4798±0.0801、0.5290±0.0528;其中NPDR组分别为0.5064±0.0843、0.4983±0.0766、0.5345±0.0529,而PDR组分别为0.4786±0.0830、0.4473±0.0778、0.5192±0.0526;正常对照组分别为0.5919±0.0704、0.6301±0.0527、0.5691±0.0169.对照组分别和NPDR组、PDR组、DR组表层视网膜、深层视网膜、脉络膜毛细血管层的黄斑血流密度比较,差异有显著统计学差异(P<0.001).NPDR组和PDR组之间黄斑血流密度在深层视网膜比较,差异有统计学意义(P=0.029),但在表层视网膜、脉络膜毛细血管层比较,差异无统计学意义(P=0.236、0.268).结论:DR患者黄斑血流密度在表层视网膜、深层视网膜和脉络膜毛细血管层均较正常对照组下降,提示黄斑区视网膜及脉络膜均存在缺血现象.OCTA可以量化黄斑血流变化的情况,为早期监测糖尿病的进展、发现DR提供有效手段.     

彩色多普勒超声对糖尿病眼球后血管血流动力学的研究

目的：探讨彩色多普勒超声对糖尿病眼球后血管血流动力学改变的作用。

方法：选取2010-06/2013-05我院收治的2型糖尿病眼病患者80例160眼作为研究组,通过眼底照相和直接检眼镜检查将研究组分为糖尿病无视网膜病变组(DNR组)、糖尿病视网膜病变非增殖期组(NPDR组)、糖尿病视网膜病变增殖期组(PDR组),选取同期眼部正常者60例120眼作为对照组,通过彩色多普勒超声对各组间视网膜中央动脉(CRA)、睫状后动脉(PCA)及眼动脉(OA)的多普勒血流参数指标进行分析。

结果：研究组与对照组在CRA、PCA和OA的血流参数上存在显著差异(P<0.05); DNR组、NPDR组和PDR组在CRA、PCA和OA的收缩期峰值流速(PSV)、舒张末期血流速度(EDV)、阻力指数(RI)与对照组存在显著差异(P<0.05),且PDR组与DNR组、NPDR组也存在显著差异(P<0.05)。

结论：通过彩色多普勒超声动态监测视网膜血流状态并对血流频谱形态进行分析,根据血流变化可以对DR病变程度进行判定,从而为治疗和预后提供参考价值。     

血清肿瘤坏死因子-α、血管内皮生长因子与糖尿病视网膜病变

目的:探讨血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平与糖尿病视网膜病变的关系。方法:将108例糖尿病患者分为糖尿病视网膜病变组(DR,60例)、非糖尿病视网膜病变组(NDR,48例),DR组又分为非增生性糖尿病视网膜病变亚组(NPDR,34例)、增生性糖尿病视网膜病变亚组(PDR,26例)。健康对照组40例。采用ELISA法检测血清TNF-α和VEGF水平,分析对比。结果:糖尿病患者血清TNF-α和VEGF水平与健康对照组比较,有显著性差异(P<0.01)。DR组血清TNF-α和VEGF水平显著高于NDR组(P<0.01);PDR组血清TNF-α和VEGF水平显著高于NPDR组(P<0.05)。结论:血清TNF-α和VEGF可能参与了DR的发生、发展,血清TNF-α、VEGF水平可反映DR病情严重程度。     

Association Between Thr21Met and Ser89Asn Polymorphisms of the Urotensin-II (UTS2) Gene, Diabetes Mellitus, and Diabetic Retinopathy

Purpose: To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish population. Methods: Total number of 280 patients with DR (nonproliferative DR 170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic controls (without DR) were included to this study. The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1 program was used for molecular modeling analysis. Results: Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele frequency (52.7% in diabetic control vs. 76.4% in PDR, P < 0.0001) frequency in PDR group were detected. However, there were no changes in genotype and allele frequencies for T21M in NPDR group. There were decreases in the S89N genotype (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were associated with NPDR patients (P < 0.001), but only MN (P < 0.001) and TS haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis showed that these two polymorphisms changed the 3D structure of UTS2, and provided interactions with neighboring residues. Conclusion: The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.     

血清PDGF-BB作为糖尿病视网膜病变生物标志物的研究

目的：研究血清中血小板源性生长因子-BB(PDGF-BB)的水平与2型糖尿病患者DR的相关性。

方法：以健康体检者为对照组(75例),糖尿病病例组分为NDR 25例、NPDR 25例和PDR 25例。用ELISA测定各组样本血清中PDGF-BB水平,并分析血清PDGF-BB与糖尿病病程、HbA1c等各项生化指标的关系,分析PDGF-BB与黄斑厚度的关系。

结果：对照组、NDR组、NPDR组、PDR组血清PDGF-BB水平各组间均有差异(F=14.259,P<0.01)。NPDR组、PDR组血清PDGF-BB水平(535.67±69.21、551.60±103.46pg/mL)均高于对照组、NDR组(400.28±44.55、409.65±50.37pg/mL)。多元回归分析血清PDGF-BB水平与空腹血糖(FPG)、甘油三酯(TG)、糖尿病病程有相关性(均P<0.05)。PDR组血清PDGF-BB水平与黄斑厚度存在相关性(r=0.613,P<0.05),对照组、NDR组、NPDR组血清PDGF-BB水平与黄斑厚度无相关性(r=0.013、0.051、0.062,均P>0.05)。

结论：血清PDGF-BB水平随着DR病变程度加重而升高,与黄斑水肿存在相关性,并与FPG、TG、糖尿病病程有相关性,可以考虑作为DR的生物学标志物。     

VEGF在PDR中的表达及作用的研究

目的:研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者血液、房水、玻璃体中血管内皮生长因子(vascular endothelial growth factor,VEGF)含量的变化,探讨VEGF与PDR的关系,为抗VEGF药物治疗的给药途径及剂量等提供理论依据。方法:采用双抗体夹心酶联免疫吸附测定法定量检测无糖尿病视网膜病变(NDR)组,单纯性糖尿病视网膜病变(BDR)组,增殖性糖尿病视网膜病变(PDR)组患者和正常对照组血浆中VEGF含量,还检测PDR患者房水、玻璃体中和正常对照组房水、玻璃体中VEGF含量,并进行综合分析。试剂盒购自美国R&D公司,其质量和灵敏度相对较高。结果:PDR组房水中VEGF含量有增高趋势,但与正常对照组比较,无统计学差异(P>0.05)。PDR患者玻璃体中VEGF含量明显增高,与正常对照组比较差异非常显著(P<0.01)。PDR组自身血浆、房水、玻璃体中VEGF含量比较有逐渐增高趋势,三者之间有显著性差异(P<0.01)。正常对照组血浆、房水、玻璃体中VEGF含量三者之间无显著性差异(P>0.05)。血浆VEGF含量在正常对照组中最高,而玻璃体中VEGF含量在PDR患者中最高。结论:PDR患者眼内尤其是玻璃体中VEGF含量大幅度增高,可能对促进DR发展恶化起了关键性的作用。在正常人,VEGF更多地存在于血浆中发挥其生物学效应。在严重DR患者中,玻璃体中异常地出现大量VEGF,推测来自缺血缺氧的视网膜,并可能有向眼前段扩散的趋势。