Genome-wide association study of Lp-PLA(2) activity and mass in the Framingham Heart Study. PLoS Genet 2010 Apr 29;6(4):e1000928
Date
05/06/2010Pubmed ID
20442857Pubmed Central ID
PMC2861686DOI
10.1371/journal.pgen.1000928Scopus ID
2-s2.0-77952343394 (requires institutional sign-in at Scopus site) 70 CitationsAbstract
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging risk factor and therapeutic target for cardiovascular disease. The activity and mass of this enzyme are heritable traits, but major genetic determinants have not been explored in a systematic, genome-wide fashion. We carried out a genome-wide association study of Lp-PLA(2) activity and mass in 6,668 Caucasian subjects from the population-based Framingham Heart Study. Clinical data and genotypes from the Affymetrix 550K SNP array were obtained from the open-access Framingham SHARe project. Each polymorphism that passed quality control was tested for associations with Lp-PLA(2) activity and mass using linear mixed models implemented in the R statistical package, accounting for familial correlations, and controlling for age, sex, smoking, lipid-lowering-medication use, and cohort. For Lp-PLA(2) activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6 x 10(-24)); CELSR2/PSRC1 on chromosome 1 (p = 3 x 10(-15)); SCARB1 on chromosome 12 (p = 1x10(-8)) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4 x 10(-8)). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA(2) mass, 12 SNPs achieved genome-wide significance, all clustering in a region on chromosome 6p12.3 near the PLA2G7 gene. Our analyses demonstrate that genetic polymorphisms may contribute to inter-individual variation in Lp-PLA(2) activity and mass.
Author List
Suchindran S, Rivedal D, Guyton JR, Milledge T, Gao X, Benjamin A, Rowell J, Ginsburg GS, McCarthy JJAuthor
David Rivedal MD Assistant Professor in the Plastic Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
1-Alkyl-2-acetylglycerophosphocholine EsteraseCardiovascular Diseases
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Polymorphism, Single Nucleotide
Risk Factors
