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- Title
Genetic variation in the renin-angiotensin system modifies the beneficial effects of ACE inhibitors on the risk of diabetes mellitus among hypertensives.
- Authors
Bozkurt, Ö.; Verschuren, W. M. M.; van Wieren-de Wijer, B. M. A.; Knol, M. J.; de Boer, A.; Grobbee, D. E.; Geerlings, M. I.; Heerdink, E. R.; Klungel, O. H.
- Abstract
The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case–control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26–0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81–2.14). The interaction OR was 3.21 (95% CI: 1.53–6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41–0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46–1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.Journal of Human Hypertension (2008) 22, 774–780; doi:10.1038/jhh.2008.62; published online 19 June 2008
- Subjects
ACE inhibitors; DIABETES; RENIN-angiotensin system; HYPERTENSION; PATIENTS; GENETIC polymorphisms
- Publication
Journal of Human Hypertension, 2008, Vol 22, Issue 11, p774
- ISSN
0950-9240
- Publication type
Article
- DOI
10.1038/jhh.2008.62