Journal Article

AGT Genetic Variation, Plasma AGT, and Blood Pressure: An Analysis of the Utah Genetic Reference Project Pedigrees

W. Scott Watkins, Andreas Rohrwasser, Andy Peiffer, Mark F. Leppert, Jean-Marc Lalouel and Lynn B. Jorde

in American Journal of Hypertension

Published on behalf of American Journal of Hypertension, Ltd.

Volume 23, issue 8, pages 917-923
Published in print August 2010 | ISSN: 0895-7061
Published online August 2010 | e-ISSN: 1941-7225 | DOI: https://dx.doi.org/10.1038/ajh.2010.83
AGT Genetic Variation, Plasma AGT, and Blood Pressure: An Analysis of the Utah Genetic Reference Project Pedigrees

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  • Neuroendocrinology and Autonomic Nervous System
  • Biochemistry
  • Endocrinology and Diabetes

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Background

Much remains unknown about the genetic factors that contribute to essential hypertension. The Utah Genetic Reference Project (UGRP) large pedigree collection provides new opportunities to study quantitative relationships between genetic variation, endophenotypes, and blood pressure.

Methods

We analyzed the relationship between common single-nucleotide polymorphisms (SNPs) and haplotypes spanning the angiotensinogen (AGT) gene and promoter region, plasma AGT levels, and systolic (SBP) and diastolic blood pressure (DBP) in 424 individuals from 41 two-generation UGRP families.

Results

Plasma AGT levels are significantly correlated among UGRP family members. Correlations are higher for males than for females. Parent–offspring correlations for plasma AGT (0.30) are higher than those for SBP (0.26) and DBP (0.17) (all P values <0.01). The additive heritability (h2) for plasma AGT is high (0.74) and substantially exceeds heritability estimates for SBP (0.26) and DBP (0.16) (all P values <0.01). Significant linkage (logarithm of the odds (LOD) >3) is found between six AGT SNPs and plasma AGT. A model that utilizes three AGT haplotype groups produces the best LOD score (5.1) that exceeds the best single SNP LOD score (3.8). Plasma AGT and blood pressure were not significantly correlated.

Conclusions

Plasma AGT levels demonstrate high heritability in 41 UGRP families. Locus-specific heritability estimates for AGT SNPs and haplotypes approach 67%, indicating that variation at AGT accounts for a large percentage of the heritability of plasma AGT. A three-way haplotype model outperforms single SNPs for quantitative linkage analysis to plasma AGT. In these predominantly normotensive individuals, plasma AGT did not correlate significantly with blood pressure.

Keywords: angiotensinogen; blood pressure; essential hypertension; haplotype; heritability; hypertension; plasma AGT

Journal Article.  3729 words.  Illustrated.

Subjects: Neuroendocrinology and Autonomic Nervous System ; Biochemistry ; Endocrinology and Diabetes

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