ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy

Abstract

Introduction:Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). Materials and methods:The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). Results: During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). Conclusion: ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.

Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis

“…[25][26][27] However, some studies in Chinese and Japanese have found there was no association between IgAN and AGT. 28,29 In 2012, Kidney Disease Improving Global Outcomes introduced the clinical practice guidelines for IgAN suggesting that RAS blockade is listed as the cornerstone of therapy for IgAN. JUN and FOS are part of the transcription factor AP-1, which regulates the expression of genes involved in proliferation, cell death, differentiation, and inflammation.…”

Genotypes of the renin–angiotensin system and glucocorticoid complications

“…Recently, Teranishi et al . reported that an I/D polymorphism in ACE contributes to variability in intrarenal angiotensin II activity . Importantly, intrarenal angiotensin II activity reflects urinary AGT, associated with increased risk for renal dysfunction in obesity and metabolic syndrome .…”

“…Recently, Teranishi et al reported that an I/D polymorphism in ACE contributes to variability in intrarenal angiotensin II activity. 29 Importantly, intrarenal angiotensin II activity reflects urinary AGT, associated with increased risk for renal dysfunction in obesity and metabolic syndrome. 30 The ACE I/D genotypes may have an association with the urinary excretion of AGT, an index of intrarenal angiotensin II status, and may be predictors for the risk of renal dysfunction in glucocorticoid-induced obesity and metabolic syndrome.…”

Recent advances in the understanding and management of IgA nephropathy

“…The beneficial effects are promoted by concomitant dietary sodium and phosphate restriction. In addition, the efficacy of RAS blockade could be modified by ACE (I/D) gene polymorphisms such that, in the future, personalized medicine could be developed using pharmacogenomics data 24 .…”