Subscribe to RSS
DOI: 10.1055/s-0030-1266730
Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity: Meta-analysis of genome-wide association studies from five community-based studies
Background: Heritability of lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme that generates pro-inflammatory and pro-atherogenic compounds in the arterial vascular wall and which may represent a therapeutic target in coronary heart disease (CHD), is incompletely understood. Methods: We sought to investigate genetic loci related to Lp-PLA2 mass or activity by conducting meta-analyses of genome-wide association (GWA) findings from five population-based studies as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, comprising 13,664 subjects. Results: In meta-analysis, two loci (PLA2G7, CYP39A1 CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 (p=2.4×10–23, log Lp-PLA2 difference per allele β: 0.043). Six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDLR2, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster (p=4.9×10–30, log Lp-PLA2 difference per allele β: –0.054). There were no significant gene-environment interactions of these eight top SNPs and age, sex, body mass index or smoking status in relation to LP-PLA2 mass or activity. Conclusions: Whereas levels of Lp-PLA2 mass and activity were associated with the gene coding for this protein, Lp-PLA2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.