Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage - Results of the Austrian Stroke Prevention Study

Background and Purpose-Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gai t disturbances. Arterial hypertension and age are the most important risk f actors. 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 age d 50 to 75 years. MARCD was defined as early confluent or confluent white m atter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was anal yzed by temporal temperature gradient gel electrophoresis and automated seq uencing. Results-We detected 4 polymorphic sites, at positions -6, -20, -153, and -2 18. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -2 18g), 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 wa s 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 t he A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining co hort (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.