The association of the angiotensinogen gene with insulin sensitivity in humans: A tagging single nucleotide polymorphism and haplotype approach

Patricia C. Underwood, Bei Sun, Jonathan S. Williams, Luminita H. Pojoga, Benjamin Raby, Jessica Lasky-Su, Steven Hunt, Paul N. Hopkins, Xavier Jeunemaitre, Gail K. Adler, Gordon H. Williams

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to clarify the association of the angiotensinogen gene (AGT) with insulin sensitivity using single nucleotide polymorphism (SNP) and haplotype analyses in a white cohort. A candidate gene association study was conducted in white persons with and without hypertension (N = 449). Seventeen SNPs of the AGT gene and their haplotypes were analyzed for an association with homeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression model accounting for age, sex, body mass index, hypertension status, study site, and sibling relatedness was used to test the hypothesis. Nine of the 17 SNPs were significantly associated with lower HOMA-IR levels. Homozygous minor allele carriers of the most significant SNP, rs2493134 (GG), a surrogate for the gain-of-function mutation rs699 (AGT p.M268T), had significantly lower HOMA-IR levels (P =.0001) than heterozygous or homozygous major allele carriers (AG, AA). Direct genotyping of rs699 in a subset of the population showed similar results, with minor allele carriers exhibiting significantly decreased HOMA-IR levels (P =.003). Haplotype analysis demonstrated that haplotypes rs2493137A|rs5050A|rs3789678G|rs2493134A and rs2004776G|rs11122576A|rs699T|rs6687360G were also significantly associated with HOMA-IR (P =.0009, P =.02), and these results were driven by rs2493134 and rs699. This study confirms an association between the AGT gene and insulin sensitivity in white humans. Haplotype analysis extends this finding and implicates SNPs rs2493134 and rs699 as the most influential. Thus, AGT gene variants, previously shown to be associated with AGT levels, are also associated with insulin sensitivity; suggesting a relationship between the AGT gene, AGT levels, and insulin sensitivity in humans.

Original languageEnglish
Pages (from-to)1150-1157
Number of pages8
JournalMetabolism: Clinical and Experimental
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Fingerprint

Angiotensinogen
Haplotypes
Single Nucleotide Polymorphism
Insulin Resistance
Genes
Homeostasis
Alleles
Hypertension
Genetic Association Studies
Body Mass Index

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

The association of the angiotensinogen gene with insulin sensitivity in humans : A tagging single nucleotide polymorphism and haplotype approach. / Underwood, Patricia C.; Sun, Bei; Williams, Jonathan S.; Pojoga, Luminita H.; Raby, Benjamin; Lasky-Su, Jessica; Hunt, Steven; Hopkins, Paul N.; Jeunemaitre, Xavier; Adler, Gail K.; Williams, Gordon H.

In: Metabolism: Clinical and Experimental, Vol. 60, No. 8, 08.2011, p. 1150-1157.

Research output: Contribution to journalArticle

Underwood, PC, Sun, B, Williams, JS, Pojoga, LH, Raby, B, Lasky-Su, J, Hunt, S, Hopkins, PN, Jeunemaitre, X, Adler, GK & Williams, GH 2011, 'The association of the angiotensinogen gene with insulin sensitivity in humans: A tagging single nucleotide polymorphism and haplotype approach', Metabolism: Clinical and Experimental, vol. 60, no. 8, pp. 1150-1157. https://doi.org/10.1016/j.metabol.2010.12.009
Underwood, Patricia C. ; Sun, Bei ; Williams, Jonathan S. ; Pojoga, Luminita H. ; Raby, Benjamin ; Lasky-Su, Jessica ; Hunt, Steven ; Hopkins, Paul N. ; Jeunemaitre, Xavier ; Adler, Gail K. ; Williams, Gordon H. / The association of the angiotensinogen gene with insulin sensitivity in humans : A tagging single nucleotide polymorphism and haplotype approach. In: Metabolism: Clinical and Experimental. 2011 ; Vol. 60, No. 8. pp. 1150-1157.
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AU - Lasky-Su, Jessica

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AU - Williams, Gordon H.

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