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.

TitleA pleiotropic QTL on 2p influences serum Lp-PLA2 activity and LDL cholesterol concentration in a baboon model for the genetics of atherosclerosis risk factors.
Publication TypeJournal Article
Year of Publication2008
AuthorsVinson, A, Mahaney, MC, Cox, LA, Rogers, J, VandeBerg, JL, Rainwater, DL
JournalAtherosclerosis
Volume196
Issue2
Pagination667-73
Date Published2008 Feb
ISSN1879-1484
Keywords1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Atherosclerosis, Cholesterol, LDL, Disease Models, Animal, Female, Male, Multivariate Analysis, Papio hamadryas, Quantitative Trait Loci, Risk Factors
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.

DOI10.1016/j.atherosclerosis.2007.07.014
Alternate JournalAtherosclerosis
PubMed ID17767937
PubMed Central IDPMC2289511
Grant ListR01 RR008781-07 / RR / NCRR NIH HHS / United States
C06 RR015456-01A1 / RR / NCRR NIH HHS / United States
R01 RR008781-078489 / RR / NCRR NIH HHS / United States
C06 RR017515-01A1 / RR / NCRR NIH HHS / United States
C06 RR017515 / RR / NCRR NIH HHS / United States
C06 RR013556-01 / RR / NCRR NIH HHS / United States
C06 RR13556 / RR / NCRR NIH HHS / United States
C06 RR014578-01 / RR / NCRR NIH HHS / United States
C06 RR013556 / RR / NCRR NIH HHS / United States
P01 HL028972 / HL / NHLBI NIH HHS / United States
R01 HL068922-05 / HL / NHLBI NIH HHS / United States
R01 HL068922 / HL / NHLBI NIH HHS / United States
R01 RR008781 / RR / NCRR NIH HHS / United States
P51 RR013986-09 / RR / NCRR NIH HHS / United States
C06 RR014578 / RR / NCRR NIH HHS / United States
R24 RR008781 / RR / NCRR NIH HHS / United States
C06 RR15456 / RR / NCRR NIH HHS / United States
P01 HL028972-25 / HL / NHLBI NIH HHS / United States
C06 RR015456 / RR / NCRR NIH HHS / United States
P51 RR013986 / RR / NCRR NIH HHS / United States