Abstract 14067: Genetic Variation in APOA5 Associates with Stepwise Increases in Plasma Triglycerides and Risk of Myocardial Infarction in 58,000 Individuals from the General Population
Objectives: Plasma triglycerides, a marker of cholesterol-containing remnant lipoproteins, are independent predictors of cardiovascular risk. Apolipoprotein A-V (apoA-V) facilitates the metabolism of triglyceride-rich lipoproteins. Although genetic variation in the apoA-V gene (APOA5) affects triglyceride levels, the association with cardiovascular risk is less clear. We tested this hypothesis. We resequenced APOA5 in individuals with the lowest 1%(n=95) and highest 2%(n=190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n=10,225). Common genetic variants which differed in frequency between the extreme triglyceride groups, were genotyped in the entire prospective CCHS. Results were validated in the cross-sectional Copenhagen General Population Study (CGPS, n=38,236), and in the case-control Copenhagen Ischemic Heart Disease Study (CIHDS, n=11,208).
Results: In the three studies individually, and in all studies combined (n=58,014) there was a per allele increase in triglyceride levels of up to 50%, and a small decrease in HDL cholesterol of up to -11%, for individuals carrying 4 versus 0 triglyceride-increasing alleles (P for trend <0.001) (Figure 1, left and middle panel). The corresponding hazard/odds ratios for MI were, 1.7 in the CCHS (P for trend =0.05), 1.6 in the CGPS (P=0.02), and 1.8 in the CIHDS (P<0.001). When combining all three studies, carrying 4 versus 0 triglyceride-increasing alleles was associated with a stepwise increase in risk of MI of 1.7(95% CI:1.3-2.2)(Figure 1, right panel), as predicted by the effect on triglyceride levels (HR=1.3, 95% CI:1.2-1.4).
Conclusion: Genetic variation in APOA5 associates with per allele increases in triglyceride levels, and with corresponding increases in risk of myocardial infarction in the general population, underscoring the importance of triglycerides as a marker for cardiovascular risk.
- © 2010 by American Heart Association, Inc.