Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy? – A systematic review

Milo A Puhan,Annalisa Perna,Johann Steurer,Lucas M Bachmann,Madlaina Scharplatz

doi:10.1186/1468-6708-6-16

Abstract

BackgroundPharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D) polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease.MethodsOur systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives) responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality.ResultsEleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes.ConclusionLack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.

Highlights

Pharmacogenetic testing to individualize Angiotensin-converting enzyme (ACE) inhibitor therapy remains controversial
Rigat et al [17] identified the insertion/deletion (I/D) polymorphism of the ACE gene, which is based on the presence or absence of a 287-bp element on intron on chromosome
This led to the hypothesis that the insertion/ deletion (I/D) polymorphism may influence the effect of ACE inhibitors on clinical outcomes

Summary

Introduction

Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. Rigat et al [17] identified the insertion/deletion (I/D) polymorphism of the ACE gene, which is based on the presence (insertion) or absence (deletion) of a 287-bp element on intron 16 on chromosome 17. Rigat et al [17] identified the insertion/deletion (I/D) polymorphism of the ACE gene, which is based on the presence (insertion) or absence (deletion) of a 287-bp element on intron on chromosome They noted that this polymorphism accounted for about 47% of the phenotypic variance for serum ACE levels. This led to the hypothesis that the I/D polymorphism may influence the effect of ACE inhibitors on clinical outcomes

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