title: Single-nucleotide polymorphisms in the TNF gene are associated with obesity-related phenotypes in vervet monkeys.
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.
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. stgray@wfubmc.edu
authors.forename: Stanton B
authors.initials: SB
authors.lastname: Gray
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.forename: Janice D
authors.initials: JD
authors.lastname: Wagner
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
mesh_terms: D000818:Animals; D001837:Body Weights and Measures / Q000662:veterinary; D002522:Chlorocebus aethiops / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D021901:DNA, Intergenic; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000662:veterinary; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000662:veterinary*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019437:Saint Kitts and Nevis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D021901:DNA, Intergenic; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol