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

Atherosclerosis. 2008 Feb;196(2):667-73. doi: 10.1016/j.atherosclerosis.2007.07.014. Epub 2007 Sep 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics*
  • Animals
  • Atherosclerosis / genetics*
  • Cholesterol, LDL / blood*
  • Disease Models, Animal
  • Female
  • Male
  • Multivariate Analysis
  • Papio hamadryas
  • Quantitative Trait Loci / genetics*
  • Risk Factors

Substances

  • Cholesterol, LDL
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase