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This Article Full Text Full Text (PDF) All Versions of this Article: jnnp.2006.109819v1 78/10/1083    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by van Rijn, M J E Articles by van Duijn, C M Search for Related Content PubMed PubMed Citation Articles by van Rijn, M J E Articles by van Duijn, C M

Polymorphisms of the renin–angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology

¹ Departments of Epidemiology and Biostatistics and Clinical Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
² Department of Neurology, Erasmus Medical Centre, Rotterdam, the Netherlands
³ Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, the Netherlands

Correspondence to:
Professor C M van Duijn, Department of Epidemiology and Biostatistics, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, the Netherlands; c.vanduijn{at}erasmusmc.nl

Methods: We genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects from the Rotterdam Scan Study. We used logistic regression and univariate analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT genotype as reference.

Results: We found that AGT–235T increased systolic (p for trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence of carotid plaques was increased 1.25-fold (95% CI 1.02–1.52) in AGT-TT carriers. There was a significant increase in mean volume deep subcortical white matter lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p = 0.008). A significant interaction was found between AGT and AT1R, further increasing the effect on periventricular and subtotal WML (p for interaction = 0.02). We found a non-significant increased risk of silent brain infarction for AGT-TT carriers and AT1R-CC carriers, but no effect on stroke.

Conclusion: We found an association between AGT and blood pressure, atherosclerosis and WML. Also, we found synergistic effects between AGT and AT1R on the development of WML. These findings raise the question of whether the renin–angiotensin system may be a therapeutic target for the prevention of cerebral white matter pathology.

Abbreviations: ACE, angiotensin converting enzyme; AGT, angiotensin gene; AT1R, angiotensin II type I receptor gene; BMI, body mass index; DBP, diastolic blood pressure; HR, hazard ratio; RAS, renin–angiotensin system; SBI, silent brain infarctions; SBP, systolic blood pressure; WML, white matter lesions