Angiotensinogen Gene Promoter Haplotype and Microangiopathy-Related Cerebral Damage
- 1 February 2001
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 32 (2), 405-412
- https://doi.org/10.1161/01.str.32.2.405
Abstract
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 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.Keywords
This publication has 33 references indexed in Scilit:
- Angiotensinogen gene and hypertension in Chinese.JCI Insight, 1998
- Effect of Renin on Brain Arterioles and Cerebral Blood Flow in RabbitsJournal of Cerebral Blood Flow & Metabolism, 1996
- Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.JCI Insight, 1996
- Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin.JCI Insight, 1994
- Cerebral white matter lesions and atherosclerosis in the Rotterdam StudyThe Lancet, 1993
- Regulatory role of brain angiotensins in the control of physiological and behavioral responsesBrain Research Reviews, 1992
- Molecular basis of human hypertension: Role of angiotensinogenCell, 1992
- Effects of Angiotensin and Atrial Natriuretic Peptide on the Cerebral CirculationJournal of Cerebral Blood Flow & Metabolism, 1992
- Molecular biology of angiotensinogen.Hypertension, 1991
- Foci of MRI signal (pseudo lesions) anterior to the frontal horns: histologic correlations of a normal findingAmerican Journal of Roentgenology, 1986