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目前国际上最主要的致盲性眼病之一,患病率日渐升高.其发生和发展与血糖水平、糖尿病病程、环境及遗传等多种因素有关.近些年来,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进展,已经筛选出了可能与之相关的数十 种基因,其中几种基因多态性已经被证实为糖尿病视网膜病变发生的独立危险因素.现将与糖尿病视网膜病变密切相关的基因多态性研究进展作一综述.     

2型糖尿病视网膜病变的视网膜光敏感度研究

目的　探讨 2型糖尿病并视网膜病变患者的视网膜光敏感度改变及其原因分析 .方法　采用国产APS -6 0 0 0B型全自动视野分析仪 ,分别对 80例 16 0眼 2型糖尿病并视网膜病变患者和对照组 80例 16 0眼进行 0°～ 90°视野视网膜光敏感度的定量检测并进行对比 .结果　糖尿病组的视网膜平均光敏感度有不同程度的下降 (p <0 .0 5 ) .结论　 2型糖尿病并视网膜病变患者的视网膜光敏感度是降低的 ,提示有光感受器的功能障碍     

2型糖尿病视网膜病变的视网膜光敏感度研究

目的探讨2型糖尿病并视网膜病变患者的视网膜光敏感度改变及其原因分析.方法采用国产APS-6000B型全自动视野分析仪,分别对80例160眼 2型糖尿病并视网膜病变患者和对照组80例160眼进行0°～90°视野视网膜光敏感度的定量检测并进行对比.结果糖尿病组的视网膜平均光敏感度有不同程度的下降(p<0.05).结论 2型糖尿病并视网膜病变患者的视网膜光敏感度是降低的,提示有光感受器的功能障碍.     

糖尿病视网膜病变基因多态性荟萃分析新进展

糖尿病视网膜病变是成年人主要致盲的眼病之一.近年来,随着糖尿病患者的不断增加,糖尿病视网膜病变的患病率也逐年递增,国内外对于此疾病的研究也越来越多,在病因学研究中,基因多态性已成为研究的热点.将多个研究进行大样本荟萃分析可以获得更有意义的结论.本文对近几年来糖尿病视网膜病变患者的基因多态性经过荟萃分析得到的有效结果进行总结.     

2型糖尿病并发视网膜病变的骨密度分析

目的：探讨2型糖尿病患者合并视网膜病变其骨密度的变化。方法：选择2型糖尿病患者111例,按糖尿病视网膜病变分为糖尿病视网膜病变组和糖尿病眼底正常对照组,采用全自动生化检测仪测定甘油三酯、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血尿酸,骨密度采由美国Norland公司XR-36型双能X线骨密度仪测定,分别测定腰椎正位(L2、L3、L4)、左侧股骨颈、大粗隆区、Ward’s三角区的骨密度。结果：1)糖尿病视网膜病变组股骨颈、大粗隆区、Ward’s三角区的骨密度低于对照组,差异有统计学意义(P<0.05);而在腰椎正位两者的差异无统计学意义(P>0.05);2)糖尿病患者的骨密度与体重指数、尿酸呈正相关,与年龄、糖尿病病程、甘油三脂、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇呈负相关。结论：2型糖尿病合并视网膜病变其骨密度降低。     

2型糖尿病患者糖尿病视网膜病变与实验室检验指标的相关性研究

目的 探讨2型糖尿病患者实验室检验指标与2型糖尿病视网膜病变(DR)进展的相关性.方法 回顾提取解放军总医院医疗大数据平台2013年至2017年51023例2型糖尿病患者数据资料,分为NDR(无DR)组、BDR(背景期DR)组和PDR(增殖期DR)组,对各组间患者的基本资料及37项实验室检验指标进行统计学比较分析.结果 BDR组和PDR组收缩压和舒张压较NDR组高;DR患者中,尤其PDR组,平均年龄更低,女性、未婚者、农村居住人口、不稳定职业者之中DR所占比率更高(均P<0.01).37项实验室检验指标水平在NDR、BDR与PDR三组间的差异均具有统计学意义(均P<0.01):①空腹及餐后2h血糖、糖化血红、血清蛋白值、三酰甘油、血尿素氮、血清肌酐、纤维蛋白原和磷脂在BDR组最高;②血清C肽值、尿肌酐值、总胆红素、直接胆红素、总蛋白、碱性磷酸酶、谷氨酰转肽酶、乳酸脱氢酶、谷丙转氨酶、谷草转氨酶值、部分活化凝血酶原时间和红细胞压积则由NDR组到BDR组、PDR组依次下降;③低密度、高密度脂蛋白值、24 h尿微量蛋白、Alb/Cr、血小板、凝血酶原活动度和血沉在组间依次增高;④白球比值在PDR组最高.Logistic回归分析中,糖化血红蛋白(OR=1.15)、血清肌酐(OR=1.13)、凝血酶原活动度(OR=1.13)、血尿素氮(OR=1.07)、纤维蛋白原(OR=1.06)和低密度脂蛋白(OR=1.05)(P<0.05)是DR的危险因素(P<0.01);而红细胞压积(OR=0.80,P<0.01)、谷氨酰胺转肽酶(OR=0.90,P<0.01)、间接胆红素(OR=0.94)、乳酸脱氢酶(OR=0.94)和年龄(OR=0.94)是DR的保护因素(P<0.05).结论 早期监测与干预2型糖尿病患者红细胞压积和代表血糖水平、肾功能、凝血功能、血脂、肝功能等的部分标志性实验室检验指标,有助于预防和延缓DR进展.     

2型糖尿病家系与尾加压素2基因多态性

目的探讨我国常州地区汉族家系2型糖尿病与尾加压素2(urotensinⅡ,UT-Ⅱ)基因rs228648多态性位点的关系。方法采用家系内外对照的病例对照研究,并设置无家族史的普通病例组,应用聚合酶链反应-限制性片段长度多态性技术,对rs228648(G/A)多态性进行基因分型。结果家系中携带AG和AA基因型者患病风险分别为GG型的1.98(95%可信区间=1.19～3.29)和2.46(95%可信区间=1.39～4.34)倍,家系病例组A等位基因频率高于内对照组及普通病例组(P=0.01)。内对照组A等位基因频率高于外对照组(P=0.001)。内对照组携带AG基因型者的胰岛素抵抗指数、胰岛素敏感指数以及胰岛初期分泌功能指数均高于GG基因型者(P<0.05)。结论rs228648多态性位点变异可能是2型糖尿病的危险因素之一,家系人群该基因变异与其胰岛功能间存在关联。     

血清补体C1q水平与2型糖尿病视网膜病变的相关性研究

目的:探讨血清补体C1q水平与2型糖尿病视网膜病变(DR)的相关性。方法:纳入2021-09—2022-09喀什地区第一人民医院内分泌科住院的2型糖尿病患者146例,根据有无并发DR分为DR组67例和糖尿病组(DM组)79例。纳入同期体检正常者81例作为正常对照(对照组)。全自动生化分析仪检测C1q、C反应蛋白(CRP)、血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的水平;采用糖化血红蛋白仪检测糖化血红蛋白(HbA1c)水平。Logistic回归分析C1q与DR的相关性,ROC曲线分析C1q对DR的诊断效能。结果:与对照组比较,DM组和DR组患者FPG、HbA1c、TC、TG(DM组除外)、LDL-C(DM组除外)、CRP和C1q水平均升高;与DM组比较,DR组血清C1q水平明显升高,差异均有统计学意义(P<0.05或P<0.01)。在充分调整了协变量后,Logistic回归分析显示,三种模型中,C1q水平均与DR的发生呈正相关。ROC曲线显示,C1q诊断DR的ROC曲线下面积为0.716(0.631...     

Resistin基因多态性与2型糖尿病相关性研究

目的：探讨中国东北汉族人resistin基因单核苷酸多态性与2型糖尿病的关系。方法：正常人80例、单纯肥胖67例、非肥胖糖尿病77例，肥胖糖尿病102例，测定空腹血糖、血清中resistin水平，并计算BMI、WHR及HOMA指数；提取外周血单核细胞中的DNA，扩增resistin基因片断之后测序，用SPSS13.0软件进行统计分析。结果：在resistin基因顺式作用元件的集中分布区检测到了9个多态位点，未发现各多态位点在四组受试者中有统计学差异；其中-638G＞A及-358 G＞A与血清resistin的水平关系较为密切。结论 抵抗素基因单核苷酸多态性可能不是2型糖尿病发病的关键因素。     

Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients

Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. In this cross sectional case-control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn-SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians.     

Association of the polymorphism in manganese superoxide dismutase gene with diabetic retinopathy in Chinese type 2 diabetic patients

OBJECTIVE: To investigate the association of the polymorphism in manganese superoxide dismutase (Mn-SOD) gene in Chinese type 2 diabetic patients with diabetic retinopathy. METHODS: The Ala(-9)Val polymorphism of the Mn-SOD gene was determined by polymerase chain reaction and direct sequencing in 198 normal control subjects and 264 patients with type 2 diabetes mellitus, among them there were 139 non-diabetic retinopathy (NDR) subjects and 125 subjects with diabetic retinopathy (DR). RESULTS: There was no statistic difference in the frequencies of VV genotype and V allele between the type 2 diabetic group and the control group. However, the frequencies of VV genotype and V allele were significantly higher in the DR group than that in the NDR group (chi-square (2)=5.015, P=0.025?chi-square (2)=10.253, P=0.001),but there was no statistic difference in the NDR group compared with the control group (P > 0.05). The presence of V allele was shown to be associated with diabetic retinopathy (OR=1.96, 95%CI: 1.29-2.97). Furthermore, the subjects carrying the VV genotype had lower serum Mn-SOD level (P=0.025) and had a tendency of higher total serum SOD activity, but this tendency had no statistic significance. CONCLUSION: The Ala(-9)Val polymorphism in the Mn-SOD gene may not be related to the etiology of type 2 diabetes, but it seems to contribute to the development of diabetic retinopathy in Chinese type 2 diabetic patients.     

The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients

 We evaluated the relationship of an alanine or valine polymorphism at amino acid sequence 16 [Val(16)Ala] of manganese superoxide dismutase (Mn-SOD) with diabetes and diabetic nephropathy in Japanese type 2 diabetic patients. Val(16)Ala genotyping of Mn-SOD was done by polymerase chain reaction-restriction fragment length polymorphism with a restriction enzyme (Bsaw I) in 478 Japanese type 2 diabetic patients and 261 nondiabetic Japanese healthy subjects. The genotype distribution of diabetic and nondiabetic subjects was then compared, and the association of genotype with diabetic nephropathy was evaluated in the diabetic patients. The allele frequency and genotype of the diabetic patients were not different from those of the healthy nondiabetic subjects. The VV type showed a significantly higher frequency in the diabetic patients with nephropathy than did the AA or VA type [VV type: normoalbuminuria 70.8%, microalbuminuria 84.8% (P = 0.0057), macroalbuminuria 84.1% (P = 0.0128)]. Furthermore, logistic regression analysis showed that this polymorphism is associated with diabetic nephropathy independently (odds ratio = 0.461925, P = 0.03). Accordingly, the Val(16)Ala polymorphism of Mn-SOD may be unrelated to the etiology of type 2 diabetes, but it seems to be associated with diabetic nephropathy in Japanese type 2 diabetic patients. Received: August 5, 2002 / Accepted: December 3, 2002 Correspondence to:Y. Tanaka     

神经源分化因子基因多态性与2型糖尿病的关联性研究

目的　探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法　运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果　 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论　 Neuro D基因多态性与早发 2型糖尿     

A pilot study of the association of manganese superoxide dismutase and glutathione peroxidase 1 single gene polymorphisms with prostate cancer and serum prostate specific antigen levels

Introduction

The aim of the study was to evaluate the potential association of single gene polymorphisms of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) with prostate cancer (PCa).

Material and methods

Manganese superoxide dismutase and glutathione peroxidase 1 genotypes and allele frequencies in 49 prostate cancer cases (PCa group) and 98 control subjects were determined. Analysis of genotypes in control group individuals were performed in two subgroups according to serum prostate-specific antigen levels: the control group (n = 49), with prostate specific antigen (PSA) level < 4 ng/ml; and the nonPCa-high PSA control group (n = 49), with serum PSA > 4 ng/ml. Determination of MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was performed using real-time polymerase chain reaction amplification.

Results

No association was found between GPX1 polymorphisms and PCa in all groups (p > 0.05). In the PCa group, the frequency of homozygote Val allele carriers was significantly higher in comparison to nonPCa-high PSA control cases. Therefore, Val/Val genotype was found significantly suspicious for PCa risk (OR = 2.48; 95% CI: 1.37–4.48; p = 0.002). Furthermore, an overall protective effect of the Ala allele of the MnSOD polymorphism on PCa risk was detected. These findings in this small Turkish population suggested that individual risk of PCa may be modulated by MnSOD polymorphism especially in patients with high PSA, but GPX1 polymorphism seemed to have no effect on PCa risk.

Conclusions

The presence of genetic variants of antioxidant enzymes could have a potential influence on genesis of prostatic malignancy.     

Oxidative stress and overexpression of manganese superoxide dismutase in patients with Alzheimer''s disease

Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Alzheimer's disease (AD) we examined the activity of the enzyme copper-zinc superoxide dismutase (CuZnSOD) in red blood cells, the levels of the mitochondrial inducible enzyme manganese superoxide dismutase (MnSOD) mRNA in lymphocytes, and the total radical-trapping antioxidant capacity (TRAP) in plasma of AD patients and in a group of age-matched non-demented controls. We found that CuZnSOD activity (P<0.01 vs. controls) was significantly increased as well as the MnSOD mRNA levels while the total antioxidant status (P<0.001 vs. controls) was decreased in AD patients. These findings support the role of oxidative alterations in the pathogenetic mechanism underlying AD neurodegeneration.     

白细胞介素6受体基因单核苷酸多态性与2型糖尿病的关联性

目的探讨甘肃地区汉族人中白细胞介素6受体基因（interleukin 6 receptor gene，IL6R）启动子-183（G→A）和第9外显子D358A的变异与2型糖尿病（type 2 diabetes mellitus，T2DM）的关联。方法随机选取无亲缘关系甘肃地区汉族人183名，其中T2DM患者87例、正常对照96名，应用聚合酶链反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism，PCR-RFLP）方法进行-183（G→A）和D358A变异的检测。结果正常对照组D358A的3种基因型频率和等位基因频率分别为AA31．2％、AC41．7％、CC27．1％、A52．1％、C47．9％，2型糖尿病组相应为AA44．8％、AC41．4％、CC13．8％、A65．5％、C34．5％，正常对照组CC基因型频率和C等位基因频率高于2型糖尿病组（χ^2=4．900，P〈0．05；χ^2=6．784，P〈0．01）。-183（G→A）3种基因型频率和等位基因频率差异无统计学意义。结论提示该基因D358A多态可能与中国人2型糖尿病关联。     

2型糖尿病患者糖尿病足的危险因素分析

目的总结分析2型糖尿病患者糖尿病足（DF）的患病情况及相关危险因素,为临床治疗和预防DF提供依据。方法选择2型糖尿病患者189例为研究对象,根据病情分为DF组和非DF组,回顾分析其性别、年龄、病程、入院时血压、空腹血糖、餐后2h血糖、糖化血红蛋白、血肌酐、尿素氮,以及尿白蛋白、糖尿病肾病、糖尿病视网膜病变、周围神经病变等因素。结果 DF所占比例为15%。DF组与非DF组相比,病程、餐后2h血糖、糖化血红蛋白、血肌酐、尿素氮、尿白蛋白、糖尿病肾病、糖尿病视网膜病变、周围神经病变等因素差异均有统计学意义（P〈0.05）。其中病程、糖尿病肾病、糖尿病视网膜病变、周围神经病变进入回归模型亦有统计学意义（P〈0.05）。结论 2型糖尿病的病程、肾病、视网膜病变、周围神经病变是DF发生的独立危险因素。     

Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients

BACKGROUND: Reactive oxygen species may contribute to the pathogenesis of asthma. Functional genetic polymorphisms of antioxidant enzymes, superoxide dismutase (SOD) and catalase are good candidates for asthma susceptibility. OBJECTIVE: To investigate the association of the manganese-containing form of SOD (MnSOD) gene at amino acid position 16 (Val16Ala) and catalase gene in the promoter at A-21T and C-262T polymorphisms and asthma in a Hong Kong Chinese population. METHODS: The association study was conducted in a case-control design in asthma patients (n=251) and healthy controls (n=316) by genotyping. The functional significance was assessed by determining erythrocyte SOD and catalase activity. RESULTS: The Val allele of MnSOD at Val16Ala and the A allele of catalase gene at A-21T were not different between patients and controls, while the C allele of catalase gene at C-262T was found to be significantly different between patients and controls (P=0.033). The less frequent variant of catalase gene (-262T) was found to be protective from the development of asthma in a Hong Kong Chinese non-smoking population (adjusted odds ratio=0.35, 0.15-0.85; P=0.017). Asthma patients had elevated erythrocyte SOD and catalase activities in comparison with healthy controls (P<0.01). However, their activities were not associated with different genotypes within healthy controls or asthma patients. CONCLUSION: This is the first report showing that SOD and catalase functional activities are not associated with their respective genetic polymorphisms but related to the presence of asthma in a Hong Kong Chinese population.