Abstract # 1975 Event # 214:

Scheduled for Saturday, August 19, 2006 08:45 AM-09:00 AM: Session 20 (Regency East #3) Oral Presentation

A QTL with Pleiotropic effects on Adipocyte Volume and Plasminogen Activator Inhibitor1 in Baboons

V. S. Voruganti1, M. E. Tejero1, J. M. Proffitt1, R. A. Bastarrachea1,2, S. A. Cole1 and A. G. Comuzzie1,2
1Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245, USA, 2Southwest National Primate Research Center, San Antonio, TX
     Plasminogen activator inhibitor 1 (PAI-1) is a major inhibitor of tissue type (tPA) and urokinase type (uPA) plasminogen activators. It has been linked to obesity and insulin resistance, and is known to modulate adipocyte differentiation. We investigated the genetic influence on PAI-1 and adipocyte-related phenotypes in baboons (Papio anubis). These animals belong to a pedigreed colony at the Southwest National Primate Research Center at the Southwest Foundation for Biomedical Research, San Antonio, TX. Omental tissue was obtained from 437 baboons, and the volume and number of collagenase-isolated adipocytes was determined. Plasma PAI-1 levels were measured by standard procedure. Genetic influence was estimated by a variance components method implemented in SOLAR. Results showed significant heritabilities for adipocyte volume (h2 = 0.21, p < 0.01), adipocyte number (h2 = 0.16, p < 0.05) and PAI-1 (h2 = 0.48, p < 0.0001). A genome-wide scan for PAI-1 revealed evidence of suggestive linkage on the baboon homolog of human chromosome 6q (D6S1056, LOD = 2.9), with age, sex and adipocyte number as covariates. A bivariate scan between PAI-1 and adipocyte volume, with the same covariates, showed a significant linkage (LOD = 4.1) on chromosome 6q near the same marker D6S1056. In summary, results show a significant genetic component to the variation of adipocyte volume, number and PAI-1, and suggest that a locus on chromosome 6q has pleiotropic effects on plasma PAI-1 levels and adipocyte volume.