Prospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2017; 8(3): 112-119
Published online Mar 15, 2017. doi: 10.4239/wjd.v8.i3.112
Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients
Neerja Aggarwal, Pawan Kumar Kare, Parul Varshney, Om Prakash Kalra, Sri Venkata Madhu, Basu Dev Banerjee, Anil Yadav, Alpana Raizada, Ashok Kumar Tripathi
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
Pawan Kumar Kare, Basu Dev Banerjee, Ashok Kumar Tripathi, Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi 110095, India
Om Prakash Kalra, Pt. B. D. Sharma University of Health Sciences, Rohtak 124001, India
Author contributions: Kalra OP, Madhu SV, Banerjee BD and Tripathi AK were involved in planning and designing the research work; Kalra OP, Madhu SV, Yadav A and Raizada A contributed to the enrollment and medication of patients; Aggarwal N, Kare PK and Varshney P were involved in the biochemical investigations and data collection; Aggarwal N carried out data interpretation and drafted the manuscript; Tripathi AK, the corresponding author, was involved in overall supervision and revision of the manuscript.
Supported by Department of Biotechnology, Government of India, New Delhi (DBT Project), No. BT/PR 4640/MED/30/716/2012.
Institutional review board statement: All procedures performed in the study involving human participants were reviewed and approved by UCMS and GTB hospital ethic committee.
Informed consent statement: Informed consent was obtained prior to enrollment from all individual participants included in the study.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest to disclose.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ashok Kumar Tripathi, PhD, Professor, Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi 110095, India. aktripathiucms@gmail.com
Telephone: +91-11-22582972
Received: July 11, 2016
Peer-review started: July 14, 2016
First decision: September 12, 2016
Revised: October 6, 2016
Accepted: November 21, 2016
Article in press: November 23, 2016
Published online: March 15, 2017
Abstract
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: Diabetic nephropathy, Angiotensin converting enzyme inhibitor therapy, Renin-angiotensin-aldosterone system gene polymorphisms, Responder, Urinary albumin/creatinine ratio, Albuminuria

Core tip: Angiotensin converting enzyme (ACE) inhibitors are used as standard therapy in patients with diabetic nephropathy (DN) and reported to have reno-protective effect in these patients; however, the response to ACE inhibitor therapy is not uniform in all patients. We investigated whether ACE I/D and angiotensinogen gene (AGT) M235T polymorphisms of genes of the renin-angiotensin-aldosterone system are associated with variable response to ACE inhibitors in DN patients. ACE inhibitor treatment in DN patients caused a significant reduction in urinary protein excretion and was found independent of ACE I/D and AGT M235T polymorphisms.