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- Title
-6A Promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree.
- Authors
Hegele, R. A.; Harris, Stewart B.; Hanley, Anthony J. G.; Sun, Fang; Connelly, Philip W.; Zinman, Bernard
- Abstract
Abstract We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely --6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the --6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT -- 6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT -- 6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of --6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT --6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.
- Subjects
ATHEROSCLEROSIS; PROMOTERS (Genetics); OJI-Cree (North American people)
- Publication
Journal of Human Genetics, 1998, Vol 43, Issue 1, p37
- ISSN
1434-5161
- Publication type
Article
- DOI
10.1007/s100380050034