A pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors.
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), the major portion of which is bound to low-density lipoprotein, is an independent biomarker of cardiovascular disease risk. To search for common genetic determinants of variation in both Lp-PLA(2) activity and LDL cholesterol (LDL-C) concentration, we assayed these substances in serum from 679 pedigreed baboons. Using a maximum likelihood-based variance components approach, we detected significant evidence for a QTL affecting Lp-PLA(2) activity (LOD=2.79, genome-wide P=0.039) and suggestive evidence for a QTL affecting LDL-C levels (LOD=2.16) at the same location on the baboon ortholog of human chromosome 2p. Because we also found a significant genetic correlation between the two traits (rho(G)=0.50, P<0.00001), we conducted bivariate linkage analyses of Lp-PLA(2) activity and LDL-C concentration. These bivariate analyses improved the evidence (LOD=3.19, genome-wide P=0.015) for a QTL at the same location on 2p, corresponding to the human cytogenetic region 2p24.3-p23.2. The QTL-specific correlation between the traits (rho(Q)=0.62) was significantly different from both zero and 1 (P[rho(Q)=0]=0.047; P[rho(Q)=1]=0.022), rejecting the hypothesis of co-incident linkage and consistent with incomplete pleiotropy at this locus. We conclude that polymorphisms at the QTL described in this study exert some genetic effects that are shared between Lp-PLA(2) activity and LDL-C concentration.
Vinson
A
A
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245, United States. avinson@sfbrgenetics.org
Mahaney
M C
MC
Cox
L A
LA
Rogers
J
J
VandeBerg
J L
JL
Rainwater
D L
DL
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D015999:Multivariate Analysis; D048529:Papio hamadryas; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors
D008078:Cholesterol, LDL; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase