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(Stroke. 2001;32:405.)
© 2001 American Heart Association, Inc.

Original Contributions

Angiotensinogen Gene Promoter Haplotype and Microangiopathy-Related Cerebral Damage

Results of the Austrian Stroke Prevention Study

Helena Schmidt, MD; Franz Fazekas, MD; Gert M. Kostner, PhD; Cornelia M. van Duijn, PhD Reinhold Schmidt, MD

From the Institute of Medical Biochemistry and Medical Molecular Biology (H.S., G.M.K.), Department of Neurology (F.F., R.S.), and MRI Center (F.F., R.S.), Karl-Franzens University, Graz, Austria, and Department of Genetic Epidemiology and Biostatistics, Erasmus University, Rotterdam, Netherlands (C.M. van D.).

Correspondence to Helena Schmidt, MD, Institute of Medical Biochemistry, Karl-Franzens University, Harrachgasse 21, A-8010 Graz, Austria. E-mail helena.schmidt{at}kfunigraz.ac.at

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.

Key Words: angiotensins • genetics • magnetic resonance imaging • small-vessel disease

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