内皮细胞型NO合成酶基因4a／4b多态性与糖尿病肾病的相关性

目的 探讨内皮细胞型NO合成酶（eNOS)基因第4内含子一个27bp的可变数目串联重复序列多态性（VNTRs,4a/4b）与中国北方汉族人2型糖尿病（DM）合并肾病（DN）的相关性。方法 运用聚合酶链反应（PCR）结合高浓度琼脂糖凝胶电泳分离和DNA测序技术，检测病程超过10年的2型DM患者（143例）和健康人（N）（85例）的eNOS基因第4内含子27bp的VNTRs(4a/4b)多态性的基因型，比较各组间的等位基因频率与基因型频率。结果 ①DM组的4a等位基因及4a4b基因型频率与N组差异无显著性（P＞0．05）。②DN＋组4a等位基因及4a4b基因型频率显著高于糖尿病非肾病患者（P＜0．05）。③SBP，HA1c，TG，TC和eNOS基因第4内含子4a/4b多态均与糖尿病肾病有关。结论 eNOS基因第4内含子4a等位基因可能是中国人2型糖尿病合并肾病的独立危险因素。

A Study of Association between Polymorphism of Endothelial Nitric Oxide Synthase Gene and Diabetic Nephropathy

Objective To investigate the association between a 27 base pair(bp) variable number of tandem repeats(VNTRs,4a/4b) polymorphism in intron 4 of the eNOS gene and diabetic nephropathy in type 2 diabetes mellitus of northern Chinese.Method A case control study for 228 Chinese subjects (including 143 type 2 diabetes mellitus with or without nephropathy and 85 normal control) was performed.The number of the 27bp VNTRs(4a/4b) alleles were determined by polymerase chain reaction(PCR) combined with 4% agarose gel electrophoresis.Result The frequency of the a allele and ab genotype in intron 4 were significantly higher in DN+ group than in DN group and control subjects (P<0.05).Multivariate logistic regression analysis showed that the blood glucose,HbA 1c ,SBP,TG,TC and the a allele in intron 4 of the eNOS gene were independent risk factors of diabetic nephropathy.Conclusion The eNOS gene VNTRs polymorphism in intron 4 may be associated with progression to diabetic nephropathy in Chinese type 2 diabetic patients.The a allele may be a risk factor for development and progression of diabetic nephropathy in chinese subjects.