ACE gene polymorphism and losartan treatment in type 2 diabetic patients with nephropathy
| Autor: | Dick de Zeeuw, Paulette A. Lyle, Jared Lunceford, Mark E. Cooper, Peter Rossing, Peggy H. Wong, Barry M. Brenner, Shahnaz Shahinfar, Hans-Henrik Parving, Giuseppe Remuzzi, Nancy Liu |
|---|---|
| Přispěvatelé: | Groningen Kidney Center (GKC) |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
INSERTION/DELETION POLYMORPHISM medicine.medical_specialty CHRONIC PROTEINURIC NEPHROPATHIES DD-GENOTYPE Urology DELETION POLYMORPHISM PROGRESSION Peptidyl-Dipeptidase A CONTROLLED-TRIAL Losartan Nephropathy chemistry.chemical_compound ANGIOTENSIN-I Clinical Research Diabetes mellitus Internal medicine medicine Clinical endpoint Humans Diabetic Nephropathies Creatinine CONVERTING-ENZYME GENE Polymorphism Genetic biology business.industry STAGE RENAL-DISEASE Angiotensin-converting enzyme General Medicine Middle Aged medicine.disease Angiotensin II Endocrinology Diabetes Mellitus Type 2 chemistry PROSPECTIVE COHORT Nephrology biology.protein Female business Angiotensin II Type 1 Receptor Blockers medicine.drug Kidney disease |
| Zdroj: | Journal of the American Society of Nephrology, 19(4), 771-779. AMER SOC NEPHROLOGY |
| ISSN: | 1533-3450 1046-6673 |
| Popis: | 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 X genotype interaction. Within the placebo group, subjects with the ID or DID genotype were more likely than those with the 11 genotype to reach the composite endpoint (by 17.5% and 38.1%, respectively, P = 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, -23.3, 28.0), 17.6% (3.8, 29.4), and 27.9% (7.0, 44.1) among those with the 11, ID, and DID 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|