Role of Angiotensin Converting Enzyme and Angiotensinogen Gene Polymorphisms in Angiotensin Converting Enzyme Inhibitor-Mediated Antiproteinuric Action in Type 2 Diabetic Nephropathy Patients

World J Diabetes. 2017 Mar 15;8(3):112-119. doi: 10.4239/wjd.v8.i3.112.


Aim: 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.

Methods: 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.

Results: 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%).

Conclusion: 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.

Keywords: Albuminuria; Angiotensin converting enzyme inhibitor therapy; Diabetic nephropathy; Renin-angiotensin-aldosterone system gene polymorphisms; Responder; Urinary albumin/creatinine ratio.