Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients.
OBJECTIVE
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%).


CONCLUSIONS
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.
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.
Neerja
N
Aggarwal
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
PK
Kare
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.
Parul
P
Varshney
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.
Om Prakash
OP
Kalra
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.
Sri Venkata
SV
Madhu
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.
Basu Dev
BD
Banerjee
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.
Anil
A
Yadav
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.
Alpana
A
Raizada
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.
Ashok Kumar
AK
Tripathi
Albuminuria; Angiotensin converting enzyme inhibitor therapy; Diabetic nephropathy; Renin-angiotensin-aldosterone system gene polymorphisms; Responder; Urinary albumin/creatinine ratio