Article

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

Horten Centre for patient oriented research, University of Zurich, Switzerland.
Current controlled trials in cardiovascular medicine (Impact Factor: 2.33). 11/2005; 6(1):16. DOI: 10.1186/1468-6708-6-16
Source: PubMed

ABSTRACT Pharmacogenetic 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.
Our 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.
Eleven 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.
Lack 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.

Download full-text

Full-text

Available from: Milo A Puhan, Sep 05, 2015
1 Follower
 · 
158 Views
 · 
67 Downloads
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insertion/deletion polymorphism of the Angiotensin I converting enzyme genetically deter-mines most of the plasma ACE activity. Modulation of ACE gene activity might have an im-portant bearing on the rate of progression of renal disease, though its exact role in the neph-ropathy of Type 2 Diabetes is far from clear. This prospective, cross-sectional, observa-tional study was designed to study correlation between Insertion/Deletion polymorphism of ACE gene in diabetic nephropathy. T2DM cases (n=30) were evaluated, regarding duration, onset and degree of of albuminuria, renal insufficiency and hypertension. All patients un-derwent detailed clinical and biochemical evaluation. Genomic DNA intron 16 of the ACE gene was amplified by polymerase chain reaction (PCR), followed by sequencing. Analysis of variance ANOVA was applied to compare. A p value < 0.05 was considered significant. All calculations were performed using SPSS-11.0. The mean age of this study group was 45.21±2.34 yrs. PCR amplification of ACE gene fragment revealed I/I, (n =8) I/D (n = 18 and D/D (n = 4), alleles.Age wise, all three groups were matched (p=0.012), micro and macro-vascular complications were more prevalent in DD type. Mmajority (75%) of patients with II allele took longer to develop overt albumiuria, having lesser hypertension, renal dysfunc-tion, and dyslipidemia than ID and DD allele (p<0.005). On the other hand, Urinary albu-min excretion (UAE), SBP, DBP, TG, S.Cr. and LDL-C were significantly higher (p<0.005), in patients of DD type than II and ID groups. This finding suggests that patients with DD allele of the ACE gene are more likely to have progressive diabetic nephropathy with most of the micro and macro-vascular complications.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Participants rated clinical marker states (CMS) to make respondents familiar with the task of preference instruments, ground their ratings in relation to other health states, and help investigators interpret patient ratings. The objective was to assess the reliability of CMS using appropriate reliability statistics. Eighty-one patients rated CMSs for mild, moderate, and severe chronic respiratory disease using the feeling thermometer (FT) and the standard gamble (SG) before and after a 3-month respiratory rehabilitation program. To assess reliability we used (a) intraclass correlation coefficients (ICC) with the variance between CMSs as signal and the variance between raters, the variance within raters, and the signal as noise; (b) scatter plots; and (c) Bland-Altman plots. ICCs were 0.47 for the FT and 0.37 for the SG. Scatter and Bland-Altman plots showed large between- and within-person variability; 64.2% and 11.3% of the CMSs ratings were in the correct order on both occasions on the FT and SG, respectively. Our results suggest moderate reliability of CMSs ratings for the FT and poor reliability for the SG, which may explain their lack of improving the SG's measurement properties. Investigators should use appropriate reliability statistics when addressing related issues.
    Journal of Clinical Epidemiology 06/2005; 58(5):458-65. DOI:10.1016/j.jclinepi.2004.07.010 · 5.48 Impact Factor
Show more