Aggarwal Neerja, Kare Pawan Kumar, Varshney Parul, Kalra Om Prakash, Madhu Sri Venkata, Banerjee Basu Dev, Yadav Anil, Raizada Alpana, Tripathi Ashok Kumar
Neerja Aggarwal, Parul Varshney, Om Prakash Kalra, Sri Venkata Madhu, Anil Yadav, Alpana Raizada, Department of Medicine, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi 110095, India.
World J Diabetes. 2017 Mar 15;8(3):112-119. doi: 10.4239/wjd.v8.i3.112.
To investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients.
In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively.
Forty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%).
ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms.
研究血管紧张素转换酶（ACE）和血管紧张素原（AGT）基因的遗传变异在糖尿病肾病（DN）患者中ACE抑制剂治疗的抗蛋白尿疗效中的作用。
在本研究中，纳入270例2型糖尿病肾病患者，用ACE抑制剂（雷米普利）治疗，并随访6个月，通过估算血清肌酐、终末期肾病和尿白蛋白/肌酐比值（ACR）来评估肾功能和白蛋白排泄情况。分别采用引物特异性聚合酶链反应（PCR）和PCR-限制性片段长度多态性（RFLP）技术对ACE I/D和AGT M235T多态性进行基因分型。
在6个月的随访中，48%的DN患者（反应者）从ACE抑制剂治疗中蛋白尿方面获益。用ACE抑制剂治疗6个月后，无论DN患者在入组时是微量白蛋白尿（≥30且<300mg/g肌酐）还是大量白蛋白尿（≥300mg/g肌酐），均观察到ACR显著降低。然而，大量白蛋白尿患者（55%）对治疗的反应更好。发现尿ACR的降低与ACE I/D和AGT M T多态性的基因型无关，尽管具有TT基因型的大量白蛋白尿患者反应增加（72%），但在统计学上无显著差异。
ACE抑制剂治疗使50%的DN患者尿ACR降低≥30%，且该反应与ACE I/D和AGT M235T多态性无关。
