Genome-wide association study of Lp-PLA2 activity and mass in the framingham heart study

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. © 2010 suchindran et al.