Clinical and genetic factors associated with lipoprotein-associated phospholipase A2 in the Framingham Heart Study

Abstract Objective To conduct an investigation of clinical and genetic correlates of lipoprotein-associated phospholipase (Lp-PLA2 ) activity and mass in a large community-based cohort. Higher circulating Lp-PLA2 predicts cardiovascular disease risk, but sources of inter-individual variability are incompletely understood. Methods We conducted stepwise regression of clinical correlates of Lp-PLA2 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-PLA2 activity; covariates associated with Lp-PLA2 mass were similar but only explained 27% of the variability. Multivariable-adjusted heritability estimates for Lp-PLA2 activity and mass were 41% and 25%, respectively. A linkage peak was observed for Lp-PLA2 activity (chromosome 6, LOD score 2.4). None of the SNPs achieved experiment-wide statistical significance, though 12 had q values