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Polymorphisms of the renin-angiotensin system are associated with blood pressure, atherosclerosis and cerebral white matter pathology
  1. M J E van Rijn (m.vanrijn{at}erasmusmc.nl)
  1. Erasmus MC, Netherlands
    1. M J Bos (m.bos{at}erasmusmc.nl)
    1. Erasmus MC, Netherlands
      1. A Isaacs (a.isaacs{at}erasmusmc.nl)
      1. Erasmus MC, Netherlands
        1. M Yazdanpanah (m.yazdanpanah{at}erasmusmc.nl)
        1. Erasmus MC, Netherlands
          1. A Arias-Vasquez (a.ariasvasquez{at}erasmusmc.nl)
          1. Erasmus MC, Netherlands
            1. B H Stricker (b.stricker{at}erasmusmc.nl)
            1. Erasmus MC, Netherlands
              1. O H Klungel (o.h.klungel{at}pharm.uu.nl)
              1. Utrecht University, Netherlands
                1. B A Oostra (b.oostra{at}erasmusmc.nl)
                1. Erasmus MC, Netherlands
                  1. P J Koudstaal (p.j.koudstaal{at}erasmusmc.nl)
                  1. Erasmus MC, Netherlands
                    1. J C Witteman (j.witteman{at}erasmusmc.nl)
                    1. Erasmus MC, Netherlands
                      1. A Hofman (a.hofman{at}erasmusmc.nl)
                      1. Erasmus MC, Netherlands
                        1. M M B Breteler (m.breteler{at}erasmusmc.nl)
                        1. Erasmus MC, Netherlands
                          1. C M van Duijn (c.vanduijn{at}erasmusmc.nl)
                          1. Erasmus MC, Netherlands

                            Abstract

                            Background: The renin-angiotensin system is involved in the development of hypertension, atherosclerosis and cardiovascular disease. We studied the association between the M235T polymorphism of the angiotensinogen gene (AGT) and the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood pressure, carotid atherosclerosis and cerebrovascular disease.

                            Methods: We genotyped over 6000 subjects of the Rotterdam Study and over 1000 subjects of 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 1.25 fold increased (95% CI: 1.02-1.52) in AGT-TT carriers. There was a significant increase in mean volume deep sub cortical white matter lesions (WML) for AGT-TT carriers (1.78 ml versus 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 whether the RAS may be a therapeutical target for the prevention of cerebral white matter pathology.

                            • atherosclerosis
                            • blood pressure
                            • polymorphism
                            • renin-Aangiotensin system
                            • white matter lesions

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