Quantitative Trait Locus Mapping of Genes That Regulate Phospholipid Transfer Activity in SM/J and NZB/BINJ Inbred Mice

Objective-Phospholipid transfer protein (PLTP), an important protein in the transfer of phospholipids between lipoprotein particles and in the remodeling of HDL, is regulated at both the transcriptional and the protein level. We performed quantitative trait locus (QTL) analysis to identify genomic loci regulating PLTP activity in mice. Methods and Results-Plasma PLTP activity was measured in 217 male F₂ progeny from a SM/J × NZB/B1NJ intercross. Two QTL for plasma PLTP activity in mice fed chow (Pltpq1 and Pltpq2) were found on chromosomes 3 (34 cM, logarithm of odds [LOD] 3.5) and 10 (66 cM, LOD 4.1); two additional QTL in mice fed atherogenic diet (Pltpq3 and Pltpq4) were found on chromosomes 9 (56 cM, LOD 4.5) and 15 (34 cM, LOD 5.0); and one QTL (Pltiq1) for the inducibility of PLTP activity was found on chromosome 4 (70 cM, LOD 3.7). Several candidate genes for these 5 QTL were tested by sequence comparison and expression studies. Conclusions-We identified five significant loci involved in PLTP activity in the mouse and provided supporting evidence for the candidacy of Nr1h4 and Apof as the genes underlying Pltpq2.