Abstract 1035: Diet-Specific Quantitative Trait Loci Affecting Variation in Serum Platelet-activating Factor Acetylhydrolase Activity in Baboons Fed Basal and Atherogenic Diets
We recently reported that activity of serum platelet-activating factor acetylhydrolase (PAF-AH), an enzyme implicated in inflammation and atherosclerosis, is significantly heritable in pedigreed baboons (Papio hamadryas) fed a low-cholesterol, low-fat (LCLF) basal diet. In this study, we tested hypotheses of interaction between genes and diet for serum PAF-AH activity. As an initial test of this hypothesis, we estimated the genetic correlation between serum PAF-AH activity measured in more than 640 pedigreed baboons fed two diets: the LCLF basal diet and a high-cholesterol, high-fat (HCHF) atherogenic diet. We found that approximately 89% of the genetic variation in serum PAF-AH activity on each diet was due to the same gene(s), while approximately 11% may be attributed to genes specific to each of the two dietary environments. To locate the unique genes or gene complexes activated in each diet, we conducted genome-wide multipoint linkage screens. In earlier analyses of serum PAF-AH activity from the LCLF diet, we detected significant evidence for a QTL on the baboon ortholog of human chromosome 2p (HSA2p) (LOD = 2.79, genome-wide p = 0.039), and suggestive evidence for a second QTL on the baboon ortholog of HSA16q (LOD = 2.03). In the current analyses of serum PAF-AH activity from the HCHF diet, we observed suggestive evidence for a previously undetected QTL located on the baboon ortholog of HSA19q (LOD = 2.44). Thus, we have detected QTLs that are specific to each of the basal and atherogenic dietary environments. We conclude that variation in serum PAF-AH activity is influenced by interaction between genes and dietary fat and cholesterol, and that serum PAF-AH should be considered a heterogeneous trait with an underlying genetic architecture dependent on dietary environment.