Obesity is an important risk factor for atherosclerosis. However, the reasons for the relationship between these disorders are still poorly understood. Evidence from body composition studies suggests that adiposity is highly correlated with several important endocrine measures including phenotypes related to glucose and lipoprotein metabolism. Little is known regarding the genes that influence adiposity and their pleiotropic effects on these endocrine parameters and on correlated risk factors for atherosclerosis such as lipoprotein phenotypes. In this Project, we will measure several adiposity-related phenotypes including total body fat (estimated using bioimpedance), and serum concentrations of several adipocyte derived endocrine factors (e.g., leptin, adiponectin, acylation stimulating protein, and TNFalpha) in pedigreed baboons. To better examine the underlying genetic determinants of variable gene expression, we will also continue to measure quantitative mRNA levels of several candidate genes (the leptin, lipoprotein lipase, and glucose transporter 4 genes) as well as three additional genes (the leptin receptor, adiponectin, and resistin genes) in biopsied omental fat tissue. We will detect and localize quantitative trait loci (QTLs) influencing adiposity-related phenotypes and test hypotheses regarding their pleiotropic effects on lipoprotein traits and genotype ? age interaction. Localization of quantitative trait loci will be accomplished via a genomic screen using candidate gene and STR polymorphisms in a single pedigree of 750 non-inbred baboons. Statistical linkage analyses will be performed using the multipoint variance component method which makes efficient use of all available information and which we have extended to accommodate the complications of inbred pedigrees. When a quantitative trait locus is found, we will utilize multivariate linkage analysis to determine if adiposity-related genes have pleiotropic effects on lipoprotein phenotypes. Finally we will attempt to identify strong positional candidate genes in the regions of promising QTLs and will use combined linkage/disequilibrium analyses and a novel Bayesian quantitative trait nucleotide analysis method to assess whether polymorphisms in these genes account for the observed linkage signal.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL028972-25
Application #
7393753
Study Section
Project Start
2007-04-01
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
25
Fiscal Year
2007
Total Cost
$376,526
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Mahaney, Michael C; Karere, Genesio M; Rainwater, David L et al. (2018) Diet-induced early-stage atherosclerosis in baboons: Lipoproteins, atherogenesis, and arterial compliance. J Med Primatol 47:3-17
Joganic, Jessica L; Willmore, Katherine E; Richtsmeier, Joan T et al. (2018) Additive genetic variation in the craniofacial skeleton of baboons (genus Papio) and its relationship to body and cranial size. Am J Phys Anthropol 165:269-285
Eichel, Kaleigh Anne; Ackermann, Rebecca Rogers (2016) Variation in the nasal cavity of baboon hybrids with implications for late Pleistocene hominins. J Hum Evol 94:134-45
Tiyasatkulkovit, Wacharaporn; Malaivijitnond, Suchinda; Charoenphandhu, Narattaphol et al. (2014) Pueraria mirifica extract and puerarin enhance proliferation and expression of alkaline phosphatase and type I collagen in primary baboon osteoblasts. Phytomedicine 21:1498-503
Chen, Shuyuan; Bastarrachea, Raul A; Roberts, Brad J et al. (2014) Successful ? cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1. Cell Cycle 13:1145-51
Higgins, Paul B; Rodriguez, Perla J; Voruganti, V Saroja et al. (2014) Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism. Am J Phys Anthropol 153:9-14
Karere, Genesio M; Glenn, Jeremy P; Birnbaum, Shifra et al. (2013) Identification of candidate genes encoding an LDL-C QTL in baboons. J Lipid Res 54:1776-85
Shi, Qiang; Hodara, Vida; Simerly, Calvin R et al. (2013) Ex vivo reconstitution of arterial endothelium by embryonic stem cell-derived endothelial progenitor cells in baboons. Stem Cells Dev 22:631-42
Shi, Qiang; Schatten, Gerald; Hodara, Vida et al. (2013) Endothelial reconstitution by CD34+ progenitors derived from baboon embryonic stem cells. J Cell Mol Med 17:242-51
Rodríguez-Sánchez, I P; Garza-Rodríguez, M L; Mohamed-Noriega, K et al. (2013) Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea, and retina. J Med Primatol 42:105-11

Showing the most recent 10 out of 291 publications