VEGF基因插入/缺失突变对糖尿病血管并发症的影响

Effect of VEGF gene insertion/deletion mutation on diabetic vascular complications

[目的]研究VEGF启动子区18-bp插入/缺失(Indel)位点对糖尿病肾病(DN)的影响。[方法]通过3%琼脂糖电泳,在DN和对照群体中检测基因型;根据分型结果统计分析基因型频率、风险值等,以及该Indel位点与DN临床指标的相关性;然后构建双荧光素酶报告载体检测VEGF的启动子活性;ELISA方法检测血浆中VECF水平。[结果]与正常组相比,等位基因型D在DN群体中的分布显著高于I;ID和DD基因型均为DN的风险指标(OR=1.14/OR=1.03);DD基因型患者的尿微量白蛋白水平极显著高于ID及II(P<0.01);DD基因型的VEGF启动子活性是II的2.71倍;DD基因型患者血浆中的VEGF含量显著高于ID和II(P<0.05)。[结论]18-bp Indel位点的DD基因型能够将VEGF的启动子活性提高2.71倍,进而促进其表达,是DN的独立风险因素。

[Objective]To study the effect of 18-bp insertion/deletion(Indel)site in VEGF promoter region on diabetic ne-phropathy(DN).[Method]Genotypes were detected in DN and control populations by 3%agarose electrophoresis;genotype frequencies,risk values,and the correlation between the Indel locus and clinical indicators of DN were statistically analyzed ac-cording to the genotyping results.The activity of VEGF promoter was detected by dual-luciferase reporting system,and the lev-el of VECF in plasma was detected by ELISA.[Result]The frequency of D allele in DN was significantly higher than that in control group,and further analysis showed that both ID and DD genotypes were risk indicators of DN(OR=1.14/0R=1.03).DD genotype was significantly higher than that in patients with ID and Ⅱ(P<0.01);DD genotypes.The activity of VEGF promoter in patients with DD genotype was 2.71-fold higher than that in Ⅱ,and the level of VEGF in plasma of patients with DD genotype was significantly higher than that of ID and Ⅱ(P<0.05).[Conclusion]The DD genotype of 18-bp Indel can increase the promoter activity of VECF by 2.71-fold,and then promote its expression,which could be considered as an inde-pendent risk factor for DN.