Journal of Pharmacogenomics & Pharmacoproteomics

Abstract

RAS Gene Polymorphisms and Renal Responsiveness to RAS Inhibition Therapy in Type 2 Diabetic Asian Indians

Balneek Singh Cheema, Harbir Singh Kohli, Rajni Sharma, Viral N Shah, Sreenivasan Iyengar, Anil Bhansali and Madhu Khullar

 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.