RAS Gene Polymorphisms and Renal Responsiveness to RAS Inhibition Therapy in Type 2 Diabetic Asian Indians
- *Corresponding Author:
- Dr. Madhu Khullar
Department of Experimental Medicine and Biotechnology
Post Graduate Institute of Medical Education and Research
Chandigarh 160012, India
E-mail: [email protected]
Received date: April 22, 2013; Accepted date: April 24, 2013; Published date: April 30, 2013
Citation: Cheema BS, Kohli HS, Sharma R, Shah VN, Iyengar S, et al. (2013) RAS Gene Polymorphisms and Renal Responsiveness to RAS Inhibition Therapy in Type 2 Diabetic Asian Indians. J Pharmacogenomics Pharmacoproteomics 4:114. doi: 10.4172/2153-0645.1000114
Copyright: © 2013 Cheema BS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Inhibitors of renin angiotensin system (RAS), ACE inhibitors (ACEI) and angiotensin II receptor blockers (ARBs), are frequently used as renal-protective agents in type 2 diabetes (T2D). However, there is significant inter individual variability in response to these drugs. In the present study, we examined the role of genetic polymorphisms in ACE, AGT and AGTR1 genes, in modulating reno-protective response to ACEI and ARB therapy in north Indian T2DM subjects, with cases having diabetic nephropathy (DN) and controls without DN. Method: 810 north Indian T2D patients treated with ACEI or ARB after diagnosis were followed up for 3 years. Percent changes in eGFR, urinary albumin excretion (UAE), serum creatinine at the end of 3 years of treatment were taken as points of renoprotective response. Result: We observed that ACE II genotype and cumulative risk score of < 1 was associated with better renoprotective response to ACEI in T2D, with normoalbuminuria (p<0.05). Whereas in T2D with micro/macroalbuminuria, DD genotype (ACE I/D) and a risk score of > 6 was associated with better renoprotective response to ARB (p<0.05). Conclusion: Our results suggest that ACE I/D genotypes individually and in interaction with other RAS SNPs modulate renoprotective efficacy of ACEI and ARB in T2D patients, depending on the status of proteinuria.