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BACKGROUND AND PURPOSE: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 most important risk factors. We assessed the association between MARCD and sequence alterations in the promoter region of the angiotensinogen (AGT) gene. METHODS:We studied 410 randomly selected community-dwelling individuals aged 50 to 75 years. MARCD was defined as early confluent or confluent white matter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was analyzed by temporal temperature gradient gel electrophoresis and automated sequencing. RESULTS:We detected 4 polymorphic sites, at positions -6, -20, -153, and -218. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -218g), B (-6:a, -20:c, -153:g, -218:g), C (-6:a, -20:c, -153:a, -218:g), D (-6:a, -20:a, -153:g, -218:g), and E (-6:a, -20:a, -153:g, -218:a). MARCD was seen in 7 subjects (63.6%) carrying 2 copies of the B haplotype (B/B), in 12 subjects (38.7%) carrying 1 copy of the B haplotype in the absence of the A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining cohort (P:<0.001). The odds ratios for the B/B and the B+/A- genotypes were 8.0 (95% CI, 2.1 to 31.1; P:=0.003) and 1.8 (95% CI, 0.8 to 4.2; P:=0.14) after adjustment for possible confounders. CONCLUSIONS:The B haplotype of the AGT promoter in the absence of the wild-type A haplotype might represent a genetic susceptibility factor for MARCD.

Original publication

DOI

10.1161/01.str.32.2.405

Type

Journal article

Journal

Stroke

Publication Date

02/2001

Volume

32

Pages

405 - 412

Addresses

Institute of Medical Biochemistry and Medical Molecular Biology, Karl-Franzens University, Graz, Austria. helena.schmidt@kfunigraz.ac.at

Keywords

Microcirculation, Brain, Humans, Cerebral Arterial Diseases, Hypertension, Angiotensins, Magnetic Resonance Imaging, Logistic Models, Odds Ratio, Risk Assessment, Cohort Studies, Age Distribution, Sex Distribution, Cerebrovascular Circulation, Gene Frequency, Haplotypes, Point Mutation, Polymorphism, Genetic, Aged, Middle Aged, Austria, Female, Male, Promoter Regions, Genetic, Genetic Testing, Genetic Linkage