内皮型一氧化氮合酶基因第4内含子中27碱基对重复序列多态性与糖尿病视网膜病变的相关性研究

目的 观察内皮型一氧化氮合酶(eNOS)基因第4内含子中27碱基对(bp)重复序列(VNTR)的插入/缺失(a/b)多态性与糖尿病视网膜病变(DR)之间的相关性.方法 321例确诊为2型糖尿病且病程在10年以上的患者为病例组,146名健康体检者为正常对照组.所有受检者均为中国汉族.病例组患者根据间接检眼镜及荧光素眼底血管造影检查结果分为DR组和无DR组(NDR组),分别为154、167例.采用聚合酶链式反应(PCR)结合8%聚丙烯酰胺凝胶电泳分离技术检测eNOS基因第4内含子中27 bp VNTR多态性,比较各组间b、a等位基因频率与b/b、a/a、b/a基因型频率,分析其与疾病的相关性.结果 eNOS基因第4内含子中27 bp VNTR b等位基凶频率在DR组显著高于NDR组(x2=4.745,P=0.029;OR=1.685,95%CI=1.050～3.905)和正常对照组(x2=6.958,P=0.008;OR=1.891,95%CI=1.172～4.437);b/b基因型频率在DR组显著高于NDR组(x2=4.811,P=0.028;OR=1.790,95%CI=1.060～4.645)和正常对照组(x2=5.203,P=0.023;OR=1.859,95%CI=1.087～4.952).结论 中国汉族2型糖尿病患者eNOS基因第4内含子b等位基因及b/b基因型与DR发生密切相关.

Abstract：

Objective To investigate the relationship between diabetic retinopathy(DR)and insertion/deletion(a/b)polymorphism of a 27 base pair variable number tandem repeat(VNTR)in intron 4of the endothelial nitric oxide synthase(eNOS)gene.Methods 321 patients of type 2 diabetes mellitus with over 10 years duration(case group)and 146 normal subjects(control group)were enrolled in this study.All the clients are Han Chinese.The case group was divided into DR subgroup(1 54 patients)and non-DR (NDR)subgroup(167 patients)according to the results of indirect ophthalmoscope and fundus fluorescent angiography.The VNTR polymorphism in eNOS gene was determined by polymerase chain reaction(PCR)combined with 8% agarose gel electrophoresis.Then the b,a allele frequency and b/b.a/a.b/a allele frequency of two groups were compared,and its correlation with diseases were analyzed.Results The b allele frequency of the VNTR in intron 4 of eNOS gene in the DR group was significantly higher than that in the NDR group(χ2=4.745,P=0.029;OR=1.685,95% CI=1.050-3.905)and control group(χ2=6.958,P=0.008;OR=1.89l,95% CI=1.172-4.437);b/b allele frequency in the DR group was also significantly higher than that in the NDR group(χ2=4.811,P=0.028;OR=1.790,95% CI=1.060-4.645)and controI group(χ2=5.203,P=0.023;OR=1.859,95% CI=1.087-4.952).Conclusions The b allele and b/b genotype in intron 4 of eNOS gene in the Han Chinese are closely related to DR.     

抗血管内皮生长因子单克隆抗体Ranibizumab联合光动力疗法治疗渗出型年龄相关性黄斑变性的临床观察

目的 观察抗血管内皮生长冈子单克隆抗体Ranibizumab玻璃体腔注射联合光动力疗法（PDT）治疗渗出型年龄相关性黄斑变性（AMD）的临床疗效和安全性.方法 回顾性系列病例研究.确诊为渗出型AMD并首次接受Ranibizumab玻璃体腔注射联合PDT治疗的患者32例（41眼）,均进行了糖尿病早期治疗研究（ETDRS）视力表、彩色眼底照像、荧光素眼底血管造影（FFA）和（或）吲哚青绿血管造影（ICGA）、光学相干断层扫描（OCT）等检查,确诊为渗出型AMD后采用PDT（光辐射率600 mW/cm2,光能量50 J/cm2,光照时间83 s）治疗,48-72 h后玻璃体腔注射Ranibizumab 0.5 mg（0.05 ml）,随后根据每个月检查情况决定是否再次治疗,重复治疗时单独注射Ranibizumab 0.5 mg,或联合PDT,或单独PDT.采用配对t检验比较治疗前后视力（ETDRS字母数）、视网膜厚度,对脉络膜新生血管（CNV）病灶渗漏情况进行计数,求百分比.结果 随诊12-39个月.在治疗后第12个月检查时,41眼ETDRS视力表字母数较治疗前平均提高9.1个字母（t=-4.14,P＜0.01）,重复Ranibizumab注射（2.0±1.1）次/眼,重复PDT治疗（0.2±0.8）次/眼.末次检查时,41眼ETDRS视力表字母数较治疗前平均提高8.9个字母（t=-3.74,P＜0.01）,重复Ranibizumab注射（2.7±1.2）次/眼,重复PDT治疗（0.3±0.7）次/眼.9眼（22%）CNV渗漏完全停止,27眼（66%）渗漏范围减少,3眼（7%）无明显变化或范围扩大,2眼（5%）有新病灶发生.OCT检查显示视网膜厚度较治疗前平均下降119.11μm（t=4.419,P＜0.01）.并发症与单独Ranibizumab或PDT治疗相比无增加.结论 Ranibizumab玻璃体腔注射联合PDT治疗渗出型AMD可使视力提高,视网膜水肿明显减轻,CNV病灶渗漏停止或减少,具有良好的疗效和较高的安全性.     

内皮型一氧化氮合酶基因第4内含子中27碱基对重复序列多态性与糖尿病视网膜病变的相关性研究

Objective To investigate the relationship between diabetic retinopathy(DR)and insertion/deletion(a/b)polymorphism of a 27 base pair variable number tandem repeat(VNTR)in intron 4of the endothelial nitric oxide synthase(eNOS)gene.Methods 321 patients of type 2 diabetes mellitus with over 10 years duration(case group)and 146 normal subjects(control group)were enrolled in this study.All the clients are Han Chinese.The case group was divided into DR subgroup(1 54 patients)and non-DR (NDR)subgroup(167 patients)according to the results of indirect ophthalmoscope and fundus fluorescent angiography.The VNTR polymorphism in eNOS gene was determined by polymerase chain reaction(PCR)combined with 8% agarose gel electrophoresis.Then the b,a allele frequency and b/b.a/a.b/a allele frequency of two groups were compared,and its correlation with diseases were analyzed.Results The b allele frequency of the VNTR in intron 4 of eNOS gene in the DR group was significantly higher than that in the NDR group(χ2=4.745,P=0.029;OR=1.685,95% CI=1.050-3.905)and control group(χ2=6.958,P=0.008;OR=1.89l,95% CI=1.172-4.437);b/b allele frequency in the DR group was also significantly higher than that in the NDR group(χ2=4.811,P=0.028;OR=1.790,95% CI=1.060-4.645)and controI group(χ2=5.203,P=0.023;OR=1.859,95% CI=1.087-4.952).Conclusions The b allele and b/b genotype in intron 4 of eNOS gene in the Han Chinese are closely related to DR.     

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。     

男性养生忌“硬熬”

有统计数据表明，每年全国约有100万男士发生心脏病，其中12％是44岁以下的男性。80％的重病男性患者承认自己长期不去医院。把小病养成大病。因此，中年男性在日常生活中，切勿犯养生保健的大忌——硬熬。[编者按]     

玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab治疗特发性脉络膜新生血管的临床观察

目的 观察玻璃体腔注射抗血管内皮生长因子(VEGF)单克隆抗体ranibizumab(商品名Lucentis)治疗特发性脉络膜新生血管(ICNV)的临床疗效和安全性.方法 经临床检查确诊的ICNV患者54例54只眼纳入研究.其中,男性24例24只眼,女性30例30只眼;年龄21～49岁,平均年龄(32.57±7.06)岁;病程6 d～3个月.采用Snellen视力表行最佳矫正视力(BCVA)、早期糖尿病视网膜病变治疗研究(EDTRS)视力表行EDTRS视力检查,同时行间接检眼镜、荧光素眼底血管造影(FFA)、光相干断层扫描(OCT)等检查.患眼治疗前BCVA眼前手动～0.6,EDTRS视力平均字母数为(32.00±16.41)个.黄斑中心视网膜厚度(CRT)平均值为(337.31±76.91) μm.玻璃体腔注射10 mg/ml的ranibizumab 0.05 ml(含ranibizumab 0.5 mg).治疗后平均随访时间(15.56±6.54)个月.首次治疗后第1个月随访检查时如发现CNV病灶扩大或有新发CNV病灶,则行再次注射治疗.对比分析治疗前后BCVA、ETDRS视力、CRT及CNV病灶渗漏变化情况.结果 首次治疗后1个月,ETDRS视力平均字母数为(48.81±16.96)个,较治疗前平均字母数增加16.81个字母,差异有统计学意义(t=-11.991,P＜0.01).视力增加＞15个字母者25只眼,占46.30％;视力减少≥1个字母者2只眼,占3.70％.OCT检查显示,CRT平均值为(227.67±91.41)μm,与治疗前CRT平均值比较,差异有统计学意义(t=12.021,P＜0.01).末次随访检查时,患眼注射次数1～4次,平均注射次数(1.59±0.71)次.ETDRS视力平均字母数为(49.20±16.60)个,较治疗前平均字母数增加17.20个字母,差异有统计学意义(t=-11.390,P＜0.01).视力增加＞15个字母者27只眼,占50.00％;视力减少≥1个字母者3只眼,占5.56％.OCT检查显示,CRT平均值为(227.69±89.30) μm,与治疗前CRT平均值比较,差异有统计学意义(t=10.872,P＜0.01).CNV渗漏完全停止者35只眼,占64.81％;渗漏范围减少者11只眼,占20.37％;渗漏无明显变化或范围扩大者6只眼,占11.11％;出现新病灶者2只眼,占3.70％.随访中未见与注射及药物有关的眼部及全身不良反应.结论 玻璃体腔注射ranibizumab治疗ICNV安全有效,可提高患眼视力,减轻黄斑水肿;其远期疗效及安全性还有待进一步观察.     

内皮型一氧化氮合酶基因第4内含子中27碱基对重复序列多态性与糖尿病视网膜病变的相关性研究

Objective To investigate the relationship between diabetic retinopathy(DR)and insertion/deletion(a/b)polymorphism of a 27 base pair variable number tandem repeat(VNTR)in intron 4of the endothelial nitric oxide synthase(eNOS)gene.Methods 321 patients of type 2 diabetes mellitus with over 10 years duration(case group)and 146 normal subjects(control group)were enrolled in this study.All the clients are Han Chinese.The case group was divided into DR subgroup(1 54 patients)and non-DR (NDR)subgroup(167 patients)according to the results of indirect ophthalmoscope and fundus fluorescent angiography.The VNTR polymorphism in eNOS gene was determined by polymerase chain reaction(PCR)combined with 8% agarose gel electrophoresis.Then the b,a allele frequency and b/b.a/a.b/a allele frequency of two groups were compared,and its correlation with diseases were analyzed.Results The b allele frequency of the VNTR in intron 4 of eNOS gene in the DR group was significantly higher than that in the NDR group(χ2=4.745,P=0.029;OR=1.685,95% CI=1.050-3.905)and control group(χ2=6.958,P=0.008;OR=1.89l,95% CI=1.172-4.437);b/b allele frequency in the DR group was also significantly higher than that in the NDR group(χ2=4.811,P=0.028;OR=1.790,95% CI=1.060-4.645)and controI group(χ2=5.203,P=0.023;OR=1.859,95% CI=1.087-4.952).Conclusions The b allele and b/b genotype in intron 4 of eNOS gene in the Han Chinese are closely related to DR.