(Hypertension. 2001;38:110.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Angiotensinogen Polymorphism M235T, Carotid Atherosclerosis, and Small-Vessel Disease-Related Cerebral Abnormalities
From the Department of Neurology (R.S., F.F., K.N., P.K., A.L.), Institute of Medical Biochemistry and Medical Molecular Biology (H.S., G.M.K.), and MRI Center (R.S., F.F., P.K.), Karl-Franzens University, Graz, Austria; and the National Institute on Aging, National Institutes of Health (L.J.L.), Bethesda, Md.
Correspondence to Dr Reinhold Schmidt, Department of Neurology, Karl-Franzens University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. E-mail reinhold.schmidt{at}kfunigraz.ac.at
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.
Key Words: angiotensinogen • genetics • carotid arteries • atherosclerosis • vessels
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