کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2893509 | 1172415 | 2009 | 7 صفحه PDF | دانلود رایگان |

ObjectiveTo 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.MethodsWe 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.ResultsSixteen 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 <0.50, and hence we expect at least 50% of these associations to be true positives. The strongest multivariable-association with Lp-PLA2 activity was found for MEF2A (rs2033547; nominal p = 3.20 × 10−4); SNP rs1051931 in PLA2G7 was nominally associated (p = 1.26 × 10−3). The most significant association to Lp-PLA2 mass was in VEGFC (rs10520358, p = 9.14 × 10−4).ConclusionsCardiovascular risk factors and genetic variation contribute to variability in Lp-PLA2 activity and mass. Our genetic association analyses need replication, which will be facilitated by web posting of our genetic association results.
Journal: Atherosclerosis - Volume 204, Issue 2, June 2009, Pages 601–607