血管紧张素I转换酶基因多态性与2型糖尿病肾病的易感性及病情发展的相关研究

Association of angiotensin I-converting enzyme gene polymorphism with the susceptibility to and progression of type 2 diabetic nephropathy

目的探讨血管紧张素Ｉ转换酶（ＡＣＥ）基因多态性与糖尿病肾病（ＤＮ）发生、发展的关系。方法用ＰＣＲ技术分别 检测９０例无ＤＮ并发症的２型糖尿病患者和１３７例不同程度蛋白尿的ＤＮ患者ＡＣＥ基因Ｉ／Ｄ多态基因型。结果ＤＮ 患者与无 ＤＮ的糖尿病患者相比，ＤＤ型基因的频率和 Ｄ等位基因的携带率明显较高（２６．８％ｖｓ １６．６７％、４８．１９％ｖｓ ３１．１１％），Ⅱ型基因的频率和 Ｉ等位基因的携带率明显较低（２８．４６％ｖｓ ５４．４４％，５１．０９％ｖｓ ６８．８９％），均有显著性差异 （Ｐ＜０．００１和Ｐ＜０．０５）；ＤＤ型患者的血压明显高于Ⅱ型基因患者。随着ＤＮ病情发展的不断加重，ＤＤ型出现频率增加， Ⅱ型出现频率减少，肾功能不全组 ＤＤ型频率（３９．１３％）显著高于临床蛋白尿组（２７．４５％）及微量蛋白尿组（２０．６３％），而 Ⅱ型频率（２１．７４％）显著低于其余两组（２７．４５％、３１．７５％）。结论 ＡＣＥ基因Ｉ／Ｄ多态性和 ＤＮ易感性密切相关。在 ＤＮ的 发展过程中，ＤＤ基因型是肾功能不全的危险因素，ＤＤ型患者预后不佳；Ⅱ型基因起保护作用，可延缓病情进展，提示 ＡＣＥ基因Ｉ／Ｄ多态性的检测可作为ＤＮ发病和病情进展的预?

Objective To elucidate whether angiotensin I-converting enzyme (ACE) gene polymorphism attributes to diabetic nephropathy (DN) or to its progression in patients with diabetes mellitus. Methods PCR technique was used to determine ACE gene polymorphism in type 2 diabetic patients, specifically, 90 without DN, 63 with microalbuminuria, 57 with clinical albuminuria and 23 with renal function insufficiency. Results Comparison between DN and DN-free group revealed the association of DD genotype with DN (x2=18.08, P<0.001), and DD genotype, along with type D allele gene, was more frequent in DN group (x2=2.41. P<0.05), in contrast to genotype Ⅱ and type I allele gene (x2=14.13 P<0.001;x2=1.57, P<0.05). Patients with DD genotype had significantly higher blood pressure than those with genotype Ⅱ. With the progression of DN, DD genotype became more frequent in patients with renal function insufficency (39.13%) than in those with clinical albuminuria (27.45%) or microalbuminuria (20.63%), but the positivity rate of if genotype, compared with the latter 2 groups (27.45% and 31 .75%), was markedly lower in patients with renal function insufficiency (21 .74%). Conclusions I/D polymorphism of ACE gene may contribute to genetic susceptibility to DN. In the development of DN, genotype DD was an important risk factor for renal function insufficiency which is indicative of unfavorable prognosis, while genotype Ⅱ is a protective factor against the progression of the disease, suggesting that examination of I/D polymorphism of ACE can be predictive of DN and its progression.