Abstract P217: Reduced Lipoprotein-Associated Phospholipase A2 Activity Levels are Linked to Apolipoprotein C3 Loss-of-Function Mutations: The Atherosclerosis Risk in Communities Study
Introduction: Higher lipoprotein-associated phospholipase A2 (LpPLA2) levels are associated with higher CHD risk. LpPLA2 is primarily transported in LDL particles and was shown to be associated positively with LDL-C but negatively with HDL-C levels. The mechanism for the negative association with HDL-C is unclear. One hypothesis is that LpPLA2 is increased in small dense LDL (sdLDL) generated with delayed clearance of lipoproteins as exhibited in atherogenic dyslipidemia. Apolipoprotein C3 (ApoC3) was shown to inhibit lipoprotein lipase’s lipolytic activity. ApoC3 loss-of-function (LOF) mutations are associated with lower triglycerides and sdLDL levels and higher HDL-C levels, reduced postprandial lipemia and reduced CHD risk. However, the association of ApoC3 LOF mutations with LpPLA2 activity is not known. We hypothesized that LpPLA2 activity levels will be lower with ApoC3 LOF mutation.
Methods: In 4453 individuals of European ancestry in the Atherosclerosis Risk in Communities (ARIC) study we examined LpPLA2 activity levels in ApoC3 LOF mutation carriers and non-carriers.
Results: There were 23 heterozygotes for ApoC3 LOF mutation in 3 variants (T5 gene based test p value=3.09 x10-3). LpPLA2 activity was inversely correlated with HDL-C (r= - 0.50) and directly correlated with LDL-C (r= 0.37) (p<0.0001 for both). There was no significant difference in total cholesterol and LDL-C levels in carriers vs. non-carriers (Table). Triglycerides, sdLDL-C levels and total cholesterol/HDL-C ratio were lower but HDL-C levels were higher in carriers than non-carriers. LpPLA2 activity was significantly lower in APOC3 carriers than in non-carriers.
Conclusion: Although there was no significant difference in LDL-C levels between ApoC3 carriers vs. non-carriers, ApoC3 LOF was associated with reduced LpPLA2 activity and sdLDL-C, supporting the concept that the inverse association between LpPLA2 and HDL-C could be related to more rapid removal of apolipoprotein B containing lipoproteins and sdLDL.
Author Disclosures: Y. Pokharel: None. W. Sun: None. L. Polfus: None. A. Folsom: None. G. Heiss: None. R. Sharrett: None. C. Ballantyne: None. R. Hoogeveen: B. Research Grant; Significant; diaDexus (to Baylor College of Medicine), Denka Seiken (to Baylor College of Medicine).
- © 2015 by American Heart Association, Inc.