title: Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel disease-related cerebral abnormalities.
abstract: The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P<0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis.
authors.affiliation: Department of Neurology, MRI Center, Karl-Franzens University, Graz, Austria. reinhold.schmidt@kfunigraz.ac.at
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: L J
authors.initials: LJ
authors.lastname: Launer
authors.forename: K
authors.initials: K
authors.lastname: Niederkorn
authors.forename: P
authors.initials: P
authors.lastname: Kapeller
authors.forename: A
authors.initials: A
authors.lastname: Lechner
authors.forename: G M
authors.initials: GM
authors.lastname: Kostner
mesh_terms: D000808:Angiotensinogen / Q000235:genetics*; D001808:Blood Vessels; D002340:Carotid Artery Diseases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013687:Telencephalon
chemical_list: D000808:Angiotensinogen