内皮细胞型NO合酶基因第7外显子894G→T点突变与糖尿病肾病相关性研究

A study of the association between polymorphism of endothelial nitric oxide synthase gene and diabetic nephropathy

目的 探讨内皮细胞型 NO合酶 (e NOS)基因第 7外显子 894 G→ T点突变与中国北方汉族人 2型糖尿病(T2 DM)合并肾病 (DN)之间的关系。方法 运用聚合酶链式反应限制性片段长度多态性技术 (PCR- RFL P) ,结合 DNA测序技术 ,检测了 2 2 8例中国北方汉族人的 e NOS基因第 7外显子 894 G→T错义突变位点的基因型 ,其中 T2 DM患者14 3例 (DN79例 ) ,健康成人 85例 ,并对各组间的等位基因频率与基因型频率进行了比较。结果 1T2 DM组的 T等位基因及 TG基因型频率与正常对照 (N)组无显著性差异 (P >0 .0 5 )。 2 DN+组 T等位基因及 TG基因型频率显著高于糖尿病非肾病患者 (P <0 .0 5 )。 3SBP、Hb A1c、TC、TG和 e NOS基因第 7外显子 894 G→T点突变均与糖尿病肾病有关 (P <0 .0 5 )。结论 e NOS基因第 7外显子 894 G→T点突变的 T等位基因可能是中国人 2型糖尿病易患肾病的独立危险因素。

Objective To investigate the association between a 894 G→T mutation at exon 7 of eNOS gene and diabetic nephropathy in type 2 diabetes mellitus of northern chinese Methods 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 894 G→T mutation alleles were determined by polymerase chain reaction and restriction fragment length polymorphism(PCR RFLP) method combined by DNA sequencing Results The frequency of the T allele and TG genotype at exon 7 were significantly higher in DN+ group than in DN group and control subjects(P<0 05) Multivariate logistic regression analysis showed that the systolic blood pressure, GHbA1c, TC,TG and the 894 G→T mutation at exon 7 of eNOS gene were risk factors for diabetic nephropathy Conclusion The T allele at exon 7 of eNOS gene are related to diabetic nephropathy in northern chinese type 2 diabetes mellitus The T allele may be a risk factor for development and progression of diabetic nephropathy in chinese subjects