Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology

  • H. Schmidt
  • F. Fazekas
  • R. Schmidt
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)


Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the best accepted risk factors for MARCD. Genes involved in blood pressure regulation, like genes encoding the proteins of the renin-angiotensin system (RAS) therefore represents good candidate genes for MARCD. Plasma angiotensinogen level is a major determinant of the RAS activity. Positive correlation between angiotensinogen gene expression and RAS activity, as well as blood pressure were observed. Common mutations described in the AGT promoter were able to alter AGT expression in cell culture. We described that 4 frequent mutations at the AGT promoter are combined in 5 haplotypes coded as A (−6:g, −20:a,−152:g, −217:g), B (−6:a, −20:c, −152:g, −217:g), C (−6:a, −20:c, −152:a, −217:g), D (−6:a, −20:a, −152:g, −217:g), and E (−6:a, −20:a, −152:g, −217:a). The B haplotype was significantly associated with MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The association was independent of hypertension, which pinpointed to a possible role of the local RAS in this relationship. Investigation of the promoter activity of the AGT gene in astrocytes suggests that expression of this gene may be modulated by the haplotype.


White Matter Hyperintensity Cerebral Small Vessel Disease Angiotensinogen Gene White Matter Hyperintensity Volume Human Angiotensinogen 


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Copyright information

© Springer-Verlag/Wien 2002

Authors and Affiliations

  • H. Schmidt
    • 1
  • F. Fazekas
    • 2
  • R. Schmidt
    • 3
  1. 1.Institute of Medical Biochemistry and Medical Molecular BiologyGrazAustria
  2. 2.Department of NeurologyKarl-Franzens UniversityGrazAustria
  3. 3.MR CentreKarl-Franzens UniversityGrazAustria

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