Abstract
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 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.
Highlights
Type 2 diabetes (T2D) is the most common cause of nephropathy, accounting for nearly 44% of renal failure cases [1,2]
Our results suggest that Angiotensin-converting enzyme (ACE) I/D genotypes individually and in interaction with other renin–angiotensin system (RAS) SNPs modulate renoprotective efficacy of Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) in T2D patients, depending on the status of proteinuria
Our results suggest that ACE I/D polymorphism was a significant modulator of response to ACEI and ARB therapy in our cohort of T2D patients, depending on their status of proteinuria
Summary
Type 2 diabetes (T2D) is the most common cause of nephropathy, accounting for nearly 44% of renal failure cases [1,2]. Studies over the past decade have shown that polymorphisms in RAS genes such as Angiotensin-converting enzyme (ACE), Angiotensinogen (AGT), and Angiotensin II type I receptor (AGTR1) may partly influence the observed inter individual variation, in response to RAS blockade [8,9,10,11,12,13,14]. It has been suggested that genetic variants, which have an association with the local tissue activity of RAS in diseased kidney, may determine the responsiveness to ACE I/ ARB [15,16]. The most common candidate gene variant proposed to date to influence response to RAS inhibition is an insertion/deletion (I/D) polymorphism in the ACE, which has been shown to influence the concentration of ACE, both in circulation and local tissue [7]. Reduction of endpoints in NIDDM with the Angiotensin II antagonist losartan (RENAAL) study, comprising 1513 patients showed
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