Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients

Weekers, Laurent; Bouhanick, Béatrice; Hadjadj, Samy; Gallois, Yves; Roussel, Ronen; Péan, Franck; Ankotché, A.; Châtellier, Gilles; Alhenc-Gélas, François; Lefèbvre, Pierre; Marre, Michel

doi:10.2337/diabetes.54.10.2961

Cited by 19 publications

(24 citation statements)

References 47 publications

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“…In T1DM with microalbuminuria treated with ACE inhibitor of lisinopril or placebo a significantly reduced albuminuria by 51.3% in carriers of II genotype compared to 7.7% in those patients with DD genotype has been reported (39). The protective effect of treatment with ACE inhibitors against development and progression of nephropathy might be through more effective reduction in glomerular capillary hydraulic pressure in patients with the II than in those with the DD genotype (40). The enhanced progression of kidney function loss in patients with DD and ID genotypes is resulting from increased internal activity of ACE and angiotensin II receptor antagonists has the greatest beneficial effects on patients with DD and ID genotypes (41).…”

Section: Ace I/d Polymorphism and Response To Therapymentioning

confidence: 99%

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 Therapymentioning

confidence: 99%

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

Rahimi¹

2012

J Nephropathol

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“…62 Many studies demonstrate importance of renin-angiotensin system in renal disorders, with clinical repercussion associated with genetically modulated ACE serum levels or due to implications in pharmacological system modulation. 12,41 Previous studies have evaluated association between renin-angiotensin system (RAS) polymorphisms and progression of renal failure secondary to a variety of diseases, but there are still several reasons for discrepancies in genetic studies of progression. Genetic basis of renal failure can be genetically complex, being likely that several genes contribute in conjunction, with individual genes showing quantitative small effects that are difficult to detect or confirm.…”

Section: Discussionmentioning

confidence: 99%

“…63 The most frequently studied is I/D polymorphism. It may modulate renal response of ACE inhibitors in terms of kidney function in patients with type 1 diabetes 12 and also has proven effects in type 2 diabetic nephropathy. 64 Other works describes influence of ACE polymorphisms as a risk factor for cardiovascular complications in long-term hemodialysis patients, 65 or effects on inflammatory cytokine levels, modulating its production and hence chronic inflammation in hemodialysis patients.…”

Section: Discussionmentioning

confidence: 99%

“…12 ACE activity can be genetically modulated by a 287-bp insertion/deletion polymorphism in intron 16 of ACE gene. 12,13 Studies using the ACE I/D polymorphism have shown a dose effect of the D allele as a genetic risk factor for circulatory dysfunction and vasoconstriction, [14][15][16][17][18] but other authors present controversial results or do not describe any significant association. [19][20][21][22][23][24][25] It is believed that this intronic (noncoding) polymorphism may be a marker for another genetic locus (or loci) with more functional significance.…”

Section: Introductionmentioning

confidence: 99%

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Análise da tendência temporal de dano renal agudo entre pacientes graves conforme polimorfi smos I/D e -262A > T da enzima conversora da angiotensina

Pedroso

Paskulin²,

Dias³

et al. 2010

J. Bras. Nefrol.

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Multiple organ failure syndrome and acute renal dysfunction share many of physiologic factors involved in their development. Recent studies correlate the susceptibility to organ dysfunction in critically ill patients with genetic inheritance. Many of them consider ACE gene could be a possible candidate to elucidate a genetic risk predisposition or a genetic factor. We aimed to examine the effects of I/D and -262A > T ACE polymorphisms in the renal function in ill southern Brazilians patients. A multi-organic worldwide known failure score, the SOFA (sequential organ failure assessment), was used to determine the basal health state at first day (ICU admission). Considering admission SOFA score and trend of renal function (measured by daily renal SOFA scores, with daily measure of serum creatinine and diuresis), we hypothesize that ACE polymorphisms could influence in the trend of renal function in ICU patients. A total of 153 critically ill adult patients (79 men) were included in this study. We monitored the patients daily during their entire ICU and post-ICU (hospital) stay (measured from the ICU admission day to a maximum of 224 days). We observed progression to renal failure (SOFA scores 3 and 4) in first seven days of ICU stay and need for dialysis. The general genotypic frequencies in our sample were II = 0.17; ID = 0.46; DD = 0.37 and AA = 0.30; AT = 0.55; TT = 0.15, and the allelic frequencies were I = 0.40; D = 0.60 and A = 0.56; T = 0.44. This is the first study to verify the influence of I/D and -262A > T ACE polymorphisms in acute renal dysfunction among critically ill patients. No significant association was found between genotypes or allele frequencies and the trend of the renal function. The I/D and -262A > T ACE polymorphisms have no significant impact on the trend of renal function during the first week of ICU stay, neither any influence in mortality in critically ill patients.

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“…This polymorphism has been postulated to affect the efficacy of ACEIs and ARBs on BP control, renal protection, and proteinuria; however, despite a large number of studies, there is no consensus, on the basis of an individual's ACE genotype, on whether ACEI or ARB treatment is preferential or should be modified. Literature can be found showing that the response to ACEIs or ARBs is not dependent on the polymorphism (28,29), is dependent on the II genotype (30,31), or is dependent on the DD genotype (32-34). It should be pointed out that differences in salt intake, underlying kidney disease, race/ethnicity, and initial level of renal function often make the interpretation and direct comparison between studies difficult.…”

Section: Therapy Based On Drug Target Variantsmentioning

confidence: 99%

Can We Personalize Treatment for Kidney Diseases?

Rovin

McKinley

Birmingham

2009

Clinical Journal of the American Society of Nephrology

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The idea of individualizing therapies to obtain optimal clinical results is not new but has only recently been applied to kidney diseases. Nonetheless, kidney disorders present a variety of opportunities to personalize medicine. Here, the heterogeneity of kidney disorders is reviewed to provide a rationale for pursuing personalized medicine. Data on adjusting therapy on the basis of pharmacogenetics/genomics and pharmacodynamics are summarized to demonstrate where the field is, and biomarker studies that reflect the future of personalized medicine are discussed. The goal of this review is to demonstrate that we can personalize therapy for kidney diseases but that considerable investment in new research will be required for personalized medicine to be routinely used in nephrology clinics. Clin J Am Soc Nephrol 4: 1670 -1676. doi: 10.2215 T he phrase personalized medicine has been used with increasing frequency in the lay press, and academia has embraced this concept by forming centers of personalized medicine within their health systems. The goal of determining the right drug, for the right patient, at the right time is not new, however, and has been actively pursued for some time in oncology using genomic tools to look for gene mutations or variations in gene expression that may affect therapy. Other disciplines, including nephrology, have joined this endeavor, although the data on personalized therapies for kidney diseases are still very preliminary. This mini-review presents these data to provide a framework for expanding research into individualized therapies for kidney diseases. Building a Case for Personalized Medicine in Kidney DiseasesThere is ample evidence that kidney disorders that are characterized by a specific constellation of clinical signs and symptoms display the molecular and biochemical heterogeneity that lends itself to individualized medicine. For example, despite similar clinical and histologic phenotypes, pediatric allograft rejection could be divided into three molecular groups by microarray analysis of total renal biopsy RNA expression (1). One of these acute rejection molecular groups was enriched for expression of B cell genes, and by immunohistochemistry, abundant B cells were found to be present in renal biopsy tissue from this subset of patients. Although the numbers were small, recovery from rejection and steroid responsiveness were significantly better in the patients who did not have B cells infiltrating their allografts. These data suggest that determining the molecular subtype of acute rejection before treatment may be used to identify patients who are likely to be steroid resistant and who may benefit from a different antirejection protocol (2).Molecular heterogeneity is also found in primary and secondary glomerular diseases. Pediatric patients who had FSGS and displayed nephrotic-range proteinuria or renal insufficiency could be differentiated from patients who did not have nephrosis or renal insufficiency, respectively, on the basis of unique renal cortical RNA expression (3...

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Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients

Cited by 19 publications

References 47 publications

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

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

Análise da tendência temporal de dano renal agudo entre pacientes graves conforme polimorfi smos I/D e -262A > T da enzima conversora da angiotensina

Can We Personalize Treatment for Kidney Diseases?

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