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Human Molecular Genetics Advance Access published online on January 13, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi060
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Human Molecular Genetics © Oxford University Press 2005; all rights reserved

Article

Haplotypes Produced from Rare Variants in the Promoter and Coding Regions of Angiotensinogen Contribute to Variation in Angiotensinogen Levels

Xiaofeng Zhu 1*, Laura Fejerman 2, Amy Luke 1, Adebowale Adeyemo 3, and Richard S. Cooper 1

1 Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, 2160 S. First Ave., Maywood, IL 60153, US
2 Department of Biological Anthropology, Oxford Unviersity, Oxford, UK
3 Department of Pediatrics, University College Hosptial, University of Ibadan, Ibadan, Nigeria; National Human Genome Research Center, College of Medicine, Howard University, Washington, DC

* To whom correspondence should be addressed.
Xiaofeng Zhu, E-mail: xzhu1{at}lumc.edu


  Abstract

The most efficient study design to map genes underlying complex traits will be determined by assumptions about whether the genetic effects are likely to be due to relatively few common variants or multiple rare variants. To examine the possibility that rare variants may influence blood pressure we sequenced a 6.8 kb region of the angiotensinogen (AGT) gene in 29 male Nigerians with high plasma AGT levels and 28 with low levels. The frequency of haplotypes produced from rare variants in the promoter and coding regions was significantly different between the two groups and it is unlikely that this difference was due to the manner in which the rare variants were selected. Further analysis suggested that most of the haplotypes produced by these rare variants are found on a haplotype background created by three common SNPs. Our study confirms in an additional trait that rare variants can influence the distribution of complex traits; whether these variants can be captured by common SNPs or haplotypes requires further investigation.


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