Abstract # 215:

Scheduled for Saturday, August 19, 2006 09:00 AM-09:15 AM: Session 20 (Regency East #3) Oral Presentation


TWO QTLs AFFECTING NORMAL VARIATION OF PLASMA PAF-AH IN BABOONS MAP TO THE BABOON ORTHOLOGS OF HUMAN CHROMOSOMES 2p and 16

A. Vinson1, D. L. Rainwater1, L. A. Cox1,2, J. Rogers1,2, J. L. VandeBerg1,2 and M. M. Mahaney1,2
1Dept. of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA, 2Southwest National Primate Research Center
line
     Plasma platelet-activating factor acetylhydrolase (PAF-AH/Lp-PLA2) is an enzyme associated with inflammation and subsequent increased risk of human cardiovascular disease. Although the structural gene for plasma PAF-AH is found on human chromosome 6 (HSA6), the contribution of this and other genes to normal variation in PAF-AH has not been previously evaluated. We measured plasma PAF-AH in 657 pedigreed baboons (Papio hamadryas) fed a basal, monkey chow diet. Using variance component decomposition methods, we estimated heritability for plasma PAF-AH to be 0.67 (p < 0.000001). Employing a genome-wide multipoint linkage analysis based on the same approach, we found significant evidence for a QTL affecting normal variation in plasma PAF-AH on baboon chromosome 13 (PHA13 ~ HSA2p) (LOD = 2.79, genome-wide p-value = 0.03944), and suggestive evidence for a second QTL on PHA20 (HSA16) (LOD = 2.03). We conclude that the contribution of genes to variation in plasma PAF-AH in baboons fed a basal diet is significant. Furthermore, variation in plasma PAF-AH levels in this study is affected primarily by genes underlying two described QTLs rather than by the plasma PAF-AH structural locus. Potential candidate genes implicated in atherosclerosis and positioned under the two QTLs include apolipoprotein B (APOB) on HSA2p, which together with plasma PAF-AH is associated with low-density lipoprotein particles, and cholesteryl ester transfer protein (CETP) on HSA16, responsible for transfer of cholesteryl esters between lipoproteins.