结缔组织生长因子基因启动子甲基化状态与糖尿病视网膜病变关系的研究

目的探讨结缔组织生长因子（CTGF）基因启动子区甲基化状态与糖尿病病人并发视网膜病变的关系，及其对血清CTGF水平的影响。方法纳入于大连大学附属中山医院内分泌科住院的糖尿病病人共计120例，根据2002年糖尿病视网膜病变国际临床分形标准，行眼底检查或者眼底荧光造影，明确糖尿病视网膜病变诊断，分为糖尿病视网膜病变组（DR组）57例，糖尿病不合并视网膜病变组（NDR组）63例，另选取大连大学附属中山医院体检中心体检的正常人58名作为健康对照组（NC组）。提取外周血白细胞DNA，应用甲基化特异PCR（MSP）检测CTGF基因启动子区甲基化状态，应用ELISA法测定各组标本中血清CTGF水平从而进行分析。结果DNA甲基化特异性PCR统计分析结果显示DR组CTGF基因启动子甲基化阳性率为24.45%，低于NDR组（42.86%）和NC组（78.95%）（P < 0.05和P < 0.01）。DR组血清CTGF水平明显高于NDR组和NC组（P < 0.01）。结论从表观遗传学角度，CTGF基因启动子低甲基化导致血清CTGF水平升高，可能是糖尿病视网膜病变发生发展的机制之一。

Study on the relationships between the promoter methylation status of CTGF gene and diabetic retinopathy

ObjectiveTo investigate the relationships between the promoter methylation status of connective tissue growth factor (CTGF) gene and diabetic retinopathy, and its effects on the serum levels of CTGF.MethodsOne hundred and twenty hospitalized diabetic patients in endocrinology department in addition select 58 normal examined subjects in physical examination center from the Affiliated Zhongshan Hospital of Dalian University were investigated.According to the international clinical classification standards of diabetic retinopathy (2002), the diabetic retinopathy in all cases were identified using the fundus examination or fluorescein angiography.The subjects were divided into the diabetic retinopathy group (DR group, n=57), diabetes without retinopathy group (NDR group, n=63), and normal control group (NC group, n=58).The DNA was extracted from the peripheral white blood cells, the promoter methylation status of CTGF gene was detected using the methylation-specific PCR (MSP), and the serum levels of CTGF in three groups were analyzed using ELISA.ResultsThe results of statistic analysis of the MSP showed that the CTGF gene promoter methylation rate in DR group was 24.45%, which was lower than that in NDR group (42.86%) and NC group (78.95%) (P < 0.05 and P < 0.01).The serum level of CTGF in DR group was signifcantly higher than that in NDR group and NC group (P < 0.01).ConclusionsIn term of epigenetics, the promoter hypomethylation status of CTGF gene can lead to the increasing of serum level of CTGF, which may be one of the mechanisms in the occurrence and development of the diabetic retinopathy.