PAI-1基因启动子区4G/5G基因多态和Enos第4内含子a/b基因多态与糖尿病肾病的相关性研究

为探讨 PAI- 1基因启动子区 4 G/ 5 G基因多态性、一氧化氮合酶 (e NOS)第 4内含子 2 7bp插入 /缺失 (a/b)多态性与糖尿病肾病 (DN)的相关性 ,采用发色底物法测定 PAI- 1活性 ;等位基因特异性引物 PCR扩增技术测定 PAI- 1基因 4 G/ 5 G多态性 ;聚合酶链反应测定 e NOS基因第 4内含子 2 7bp的 a/ b多态性。结果显示 ,Hb A1c、SBP、TC、e NOS基因第 4内含子 a/ b多态均属 DN的独立危险因素。早期糖尿病肾病组 (DN+组 ) a等位基因及 ab基因型频率显著高于糖尿病非肾病组 (DN-组 ) (P<0 .0 5 )。DN+组血浆 PAI- 1活性明显高于 DN-组 (P<0 .0 5 ) ;4 G纯合子组 PAI- 1活性明显高于 4 G/ 5 G杂合子及 5 G纯合子组 (P<0 .0 0 5 )。2型糖尿病患者中 ,4 G纯合子和a/ b杂合子携带者 DN的相对风险明显增加 (P<0 .0 5 ) ,4 G杂合子携带者 DN的相对风险增加不明显 (P>0 .0 5 )。当 a/ b杂合子和 4 G纯合子基因多态并存时 DN的发病风险明显增加。认为 PAI- 1基因启动子区 4 G/ 5 G基因多态、e NOS基因第 4内含子 a/ b多态与 DN的发生、发展有关。两种基因多态同时存在时 ,DN的发病风险明显增加

Correlation between a 27 repeat polymorphism in intron 4 of the eNOS gene and PAI-1 gene promoter polymorphism and diabetic nephropathy

To investigate the correlation between 27 base pair(bp) repeat polymorphism in intron 4 of the eNOS gene and PAI 1 promoter 4G/5G polymorphism and diabetic nephropathy in type 2 diabetes mellitus.143 patients with type 2 diabetes mellitus with or without nephropathy were studied.The polymorphism of the 27bp repeat alleles was determined by PCR.The 4G/5G polymorphism in the PAI 1 gene promoter region were genotyped by allele specific PCR.Results showed the blood glucose,HbAlc,SBP,TC,27 bp repeat polymorphism in intron 4 of the eNOS gene were independent risk factors for diabetic nephropathy.The frequency of the a allele and a/b genotype in intron 4 were significantly higher in DN(+)group than in DN(-)group and control subjects(P<0.05).The plasma PAI 1 activity in DN(+)group was higher than that in DN(-)group(P<0.05);PAI 1 activity was significantly higher in 4G allele homozygous than those in 4G/5G heterozygous and 5G homozygous(P<0.05).The odds ratio of diabetic nephropathy was significantly higher in 4G allele homozygous and in a/b heterozygous,while there was no difference in 4G/5G heterozygous.Diabetic patients with coexistence of the a/b heterozygous and 4G alleles had a higher incidence of diabetic nephropathy(P<0.05)than those with only one of the two allele or without any of the two alleles.These suggest 27 bp repeat polymorphism in intron 4 of the eNOS gene and PAI 1 gene promoter 4G/5G polymorphism are related to diabetic nephropathy in Chinese type 2 diabetes.The risk of developing diabetic nephropathy was significantly increased if patients with a/b heterozygous and 4G allele homozygous simultaneously.