Clinical and genetic factors associated with lipoprotein-associated phospholipase A"2 in the Framingham Heart Study

Atherosclerosis 204(2):7 (2009) PMID 19135199

Objective: To conduct an investigation of clinical and genetic correlates of lipoprotein-associated phospholipase (Lp-PLA"2) activity and mass in a large community-based cohort. Higher circulating Lp-PLA"2 predicts cardiovascular disease risk, but sources of inter-individual variability are incompletely understood. Methods: We conducted stepwise regression of clinical correlates of Lp-PLA"2 in four Framingham Heart Study cohorts (n=8185; mean age 50+/-14 years, 53.8% women, 9.8% ethnic/racial minority cohort). We also conducted heritability and linkage analyses in Offspring and Generation 3 cohorts (n=6945). In Offspring cohort participants we performed association analyses (n=1535 unrelated) with 1943 common tagging SNPs in 233 inflammatory candidate genes. Results: Sixteen clinical variables explained 57% of the variability in Lp-PLA"2 activity; covariates associated with Lp-PLA"2 mass were similar but only explained 27% of the variability. Multivariable-adjusted heritability estimates for Lp-PLA"2 activity and mass were 41% and 25%, respectively. A linkage peak was observed for Lp-PLA"2 activity (chromosome 6, LOD score 2.4). None of the SNPs achieved experiment-wide statistical significance, though 12 had q values 2 activity and mass. Our genetic association analyses need replication, which will be facilitated by web posting of our genetic association results.