Single-Nucleotide Polymorphisms in the TNF Gene Are Associated With Obesity-Related Phenotypes in Vervet Monkeys

Authors

  • Stanton B. Gray,

    1. Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
    2. Center for Genetics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Carl D. Langefeld,

    1. Department of Public Health Sciences, Section on Statistical Genetics and Bioinformatics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Julie T. Ziegler,

    1. Department of Public Health Sciences, Section on Statistical Genetics and Bioinformatics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Gregory A. Hawkins,

    1. Center for Genetics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Janice D. Wagner,

    1. Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
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  • Timothy D. Howard

    Corresponding author
    1. Center for Genetics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
      (stgray@wfubmc.edu)
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(stgray@wfubmc.edu)

Abstract

Tumor necrosis factor (TNF) promoter single-nucleotide polymorphisms (SNPs) have been extensively characterized in humans, with numerous reports of associations with obesity-related phenotypes as well an array of infectious, immune-mediated, and inflammatory disease phenotypes. Controlling for the multitude of environmental risk factors in human studies has been a major confounder of efforts to elucidate the role and relative contribution of TNF promoter SNPs. As part of an ongoing initiative to further genetically and phenotypically characterize the St Kitts-origin vervet monkey (Chlorocebus aethiops ssp.) as an animal model of human obesity, we have conducted association analyses between TNF SNPs and previously defined obesity-related phenotypes in 265 pedigreed vervets. We report eight SNPs (−809G, −756A, −352C, −322A, +1285T, +2133T, +2362A, +2405), all contained within the same haplotype block and comprising a single haplotype, to be significantly associated with BMI, waist circumference, total plasma cholesterol (P < 0.05), and high-density lipoprotein-cholesterol (HDL-C) (P < 0.01). This study provides additional validation of the St Kitts-origin vervet model of obesity by demonstrating genetic associations analogous to that shown in humans.

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