Year-end Sale % OFF 
Abstract
Lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2 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-PLA2 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-PLA2 activity, polymorphisms at four independent loci reached genome-wide significance, including the APOE/APOC1 region on chromosome 19 (p = 6×10−24); CELSR2/PSRC1 on chromosome 1 (p = 3×10−15); SCARB1 on chromosome 12 (p = 1×10−8) and ZNF259/BUD13 in the APOA5/APOA1 gene region on chromosome 11 (p = 4×10−8). All of these remained significant after accounting for associations with LDL cholesterol, HDL cholesterol, or triglycerides. For Lp-PLA2 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-PLA2 activity and mass.
Highlights
It is increasingly recognized that inflammation plays an important role in the development of atherosclerotic cardiovascular disease
Studies in animal models with human-like lipoprotein metabolism have suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) activity contributes to atherosclerosis development, and epidemiological studies have presented evidence that circulating concentrations of Lp-PLA2 or elevated activity of the enzyme are associated with cardiovascular disease after adjusting for established risk factors [1,2,3]
To gain insight into genetic variants that control Lp-PLA2 activity and mass, we conducted a genome-wide association study using data from the Framingham Heart Study released through the SHARe Project
Summary
It is increasingly recognized that inflammation plays an important role in the development of atherosclerotic cardiovascular disease. Studies in animal models with human-like lipoprotein metabolism have suggested that Lp-PLA2 activity contributes to atherosclerosis development, and epidemiological studies have presented evidence that circulating concentrations of Lp-PLA2 or elevated activity of the enzyme are associated with cardiovascular disease after adjusting for established risk factors [1,2,3]. This has led to the recent development of an orally active Lp-PLA2 inhibitor currently in clinical trials for cardiovascular prevention [3]. Small dense LDL are found in the metabolic syndrome, which is associated with high Lp-PLA2 activity [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
