Association between evolutionary history of angiotensinogen haplotypes and plasma levels
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Over the last decade, considerable effort has been invested in studying the associations between angiotensinogen (AGT) variants, AGT plasma levels and high blood pressure. Evidence accumulated to date consistently supports the relationship between the AGT locus and the protein level, while an influence on blood pressure has been difficult to establish; in both instances the predisposing molecular variants are not fully defined. An evolutionary approach, taking into account the phylogenetic relationship between all the polymorphisms at this locus, may improve our understanding of the genetic nature of these quantitative phenotypes. Accordingly we sequenced a 6.8 kb region of the AGT gene in 57 Nigerian individuals (29 with high AGT plasma levels and 28 with low AGT plasma levels). Haplotypes were grouped into seven major haplogroups and their phylogenetic relationship was established. The association between haplogroups and AGT plasma levels was investigated. A significant linear correlation was detected between haplogroup genetic distance and AGT levels, suggesting a nonrandom accumulation of risk-associated mutations during the evolutionary history of the AGT gene.
KeywordsGenetic Distance Angiotensinogen 235T Variant Average Excess Major Haplogroups
This research was supported by grants from the NHLBI (HL45508; HL 47910). We would also like to thank the residents of Igbo-Ora, Nigeria for their willing participation in this research project. Donghui Kan assisted with statistical programming.
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