Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients – interaction with ACE insertion/deletion polymorphism

So, Wing‐Yee; Ma, Rong; Ozaki, Risa; Tong, Peter C.Y.; Ng, Maggie C. Y.; Ho, Chung-Shun; Lam, Christopher Wai‐Kei; Chow, Chun Chung; Chan, Wing-Bun; Kong, Alice Pik‐Shan; Chan, Juliana C.N.

doi:10.1038/sj.ki.5000097

Cited by 59 publications

(52 citation statements)

References 30 publications

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“…It has been demonstrated that T2DM patients with normoor micro-albuminuria carrying I allele had a better response to ACE inhibitor therapy compared to those patients with D allele. While, in T2DM with overt nephropathy and D allele there was a better response to angiotensin II receptor antagonists therapy compared to I allele (5,12,37,38). Similar comparable results were obtained in T1DM (39).…”

Section: Ace I/d Polymorphism and Response To Therapysupporting

confidence: 76%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

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Implication for health policy/practice/research/medical education:The presence of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with highest systemic and renal ACE levels, compared with the lowest ACE activity in carriers of II genotype. Most studies confirmed that ACE I/D polymorphism is involved in the susceptibility to overt nephropathy with protective role of ACE II genotype against the disease in both type 1 and 2 diabetes mellitus. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Results:The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. Conclusions: In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.Review Article

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Section: Ace I/d Polymorphism and Response To Therapysupporting

confidence: 76%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

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“…Consistent with data in type I diabetes, the study by So et al in 2089 Chinese patients with normoalbuminuria, microalbuminuria, or macroalbuminuria (44) found that over a median period of 44.6 mo, ACE inhibitor therapy decreased mortality, ESKD, or progression to estimated GFR Ͻ15 ml/min per 1.73 m 2 more effectively in II and ID than in DD carriers. This was the only study in type II diabetes with adequate power and follow-up.…”

Section: Ace Inhibitorssupporting

confidence: 70%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.

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“…7,8 Furthermore, a reduced anti-albuminuric response to ACE inhibition has been demonstrated in type 1 diabetic patients with the D allele. 25 So et al 26 recently reported a large long-term observational study of a consecutive cohort of 2089 Chinese type 2 diabetic patients genotyped for the ACE/ID gene polymorphism. The study revealed that DD genotype enhanced the risk of a doubling of baseline serum creatinine concentration and ESRD.…”

Section: Discussionmentioning

confidence: 99%

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

Parving¹,

Zeeuw²,

Cooper³

et al. 2008

Journal of the American Society of Nephrology

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Losartan treatment reduced renal outcomes in proteinuric patients with type 2 diabetes in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. It is unknown whether an insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene predicts renal outcomes and death and influences the effect of losartan in these patients. Pharmacogenetic analyses were performed comparing losartan with placebo administered with conventional blood pressure-lowering therapy in 1435 (95%) of the 1513 RENAAL study patients. The primary endpoint was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease (ESRD) or death. Cox regression models were stratified on baseline proteinuria and included treatment, geographic region, ACE/ID genotype, and treatment ϫ genotype interaction. Within the placebo group, subjects with the ID or DD genotype were more likely than those with the II genotype to reach the composite endpoint (by 17.5% and 38.1%, respectively, P ϭ 0.029) or its individual components. Within the losartan group, genotype did not correlate with reaching the composite endpoint. Compared with placebo, however, losartan reduced the risk of reaching the composite endpoint by 5. 8% (95% confidence interval, Ϫ23.3, 28.0), 17.6% (3.8, 29.4), and 27.9% (7.0, 44.1) among those with the II, ID, and DD genotypes, respectively. Similar trends were demonstrated for the individual endpoints. In conclusion, proteinuric type 2 diabetic patients with the D allele of the ACE gene have an unfavorable renal prognosis, which can be mitigated and even improved by losartan.

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Angiotensin-converting enzyme (ACE) inhibition in type 2, diabetic patients – interaction with ACE insertion/deletion polymorphism

Cited by 59 publications

References 30 publications

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy

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