2型糖尿病肾病中ACE基因型和ACEI疗效关系的研究

Relationship between ACE gene polymorphism and therapeutic responsiveness of ACEI in type 2 diabetic nephropathy

目的 探讨血管紧张素转换酶抑制剂 (ACEI)治疗三种血管紧张素酶 (ACE)基因型的2型糖尿病肾病的疗效有无差异 ,判断 ACE基因插入 /缺失 (I/ D)多态性对 ACEI治疗 2型糖尿病肾病的疗效有无预测作用。 方法 6 8例 2型糖尿病临床肾病患者 ,用胰岛素控制血糖 ,福辛普利 2 0mg/ d治疗 8周 ;用药前所有受试者以 PCR方法检测 ACE基因 I/ D多态性 ,并据其分为三组 ,ACE基因 II型 33例、ID型 2 1例、DD型 14例 ,于治疗前后分别测定血清 ACE活性、尿白蛋白排泄率(UAE)、血清肌酐 (SCr)、糖化血红蛋白 (Hb A 1c)、体重指数 (BMI)和平均动脉压 (MAP)。 结果 治疗前三组年龄、BMI、MAP、Hb A1c、Scr、U AE差异均无显著性 (P>0 .0 5 ) ,血清 ACE活性在 DD型组最高、ID组次之、II型组最低 (P<0 .0 5 ) ;福辛普利治疗 8周后 ,三组受试者 BMI、Scr无明显变化 ,MAP、Hb A1c均有下降 ,但三组间变化差异无显著性 (P>0 .0 5 ) ;U AE、血清 ACE活性下降的百分率在 DD型组最高、ID型组次之、II型组最低 ,差异有显著性 (P<0 .0 5 ) ;多因素相关分析 UAE降低与MAP、Hb A1c下降无相关 ,与血清 ACE活性的下降相关 (r=0 .2 99,P<0 .0 5 )。 结论 ACEI治疗 2型糖尿病肾病疗效 ,在 ACE基因 DD型最好、ID型次之、II型最差 。

Objective To clarify the relationship between angiotensin 1 converting enzyme (ACE) gene insertion/deletion(I/D) polymorphism and therapeutic responsiveness of ACE inhibitor (ACEI) in type 2 diabetic nephropathy. Methods 68 type 2 diabetic patients with overt nephropathy were recruited from our clinic. Before entry, previously used ACEI, diuretic agents and other anti hypertension agents were withdrawn for 10 days. Patients were classified into three groups according to ACE genotypes and treated with Fosinopril for 8 weeks. Various clinical parameters including age, body mass index (BMI), 24 hour urinary excretion of albumin (UAE), serum ACE activity, serum creatinine, HbA1c and mean arterial pressure (MAP) were measured in the pre and post treatment. The I/D polymorphism of ACE gene was identified by polymerase chain reaction (PCR). Serum ACE activity was determined using spectrophotometry. Results The distribution of II, ID and DD genotypes of ACE gene in 68 cases with diabetic nephropathy were 33,21 and 14 cases. There were no significant differences in the clinical parameters such as age, BMI, MAP, HbA1c, serum creatinine and UAE among three groups ( P >0.05). Serum ACE activity was the highest in DD genotype, higher in ID genotype and the lowest in II genotype ( P <0 05). After 8 weeks treatment using Fosinopril, there was no significant difference in the reduction of MAP and HbA1c. The reductions in UAE and serum ACE activity were the highest in DD genotype, higher in ID genotype and lowest in II genotype. There were statistically significant correlations between the reductions of UAE and serum ACE activity ( r=0.299,P <0.05). Conclusion The results suggest there was association between ACE gene I/D polymorphism and therapeutic responsiveness of ACEI in type 2 diabetic nephropathy. The examination of ACE gene polymorphism is helpful for the prediction of the therapeutic efficacy of ACEI in type 2 diabetic nephropathy.