INFLUENCE OF THE APOLIPOPROTEIN A5 LOCUS ON PLASMA TRIGLYCERIDE, REMNANT-LIKE PARTICLES, AND LIPOPROTEIN SUBFRACTION CONCENTRATIONS -IMPLICATION FOR CARDIOVASCULAR RISK IN THE FRAMINGHAM HEART STUDY

Authors: Lai, Chao Qiang; DEMISSIE, SERKALEM - SCH OF PUBLIC HEALTH, BU; CUPPLES, ADRIENNE - SCH OF PUBLIC HEALTH, BU; ZHU, YUEPING - USDA-HNRCA; ADICONIS, XIAN - USDA-HNRCA; Parnell, Laurence; CORELLA, DOLORES - USDA-HNRCA; Ordovas, Jose

Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/19/2004
Publication Date: 9/1/2004
Citation: Lai, C., Demissie, S., Cupples, A., Zhu, Y., Adiconis, X., Parnell, L.D., Corella, D., Ordovas, J.M. 2004. Influence of the apolipoprotein a5 locus on plasma triglyceride, remnant-like particles, and lipoprotein subfraction concentrations -implication for cardiovascular risk in the framingham heart study. Arteriosclerosis Thrombosis and Vascular Biology. 2004; 45: 2096-2105

Interpretive Summary: High concentrations of fat in the blood are important hallmarks of heart disease risk. Therefore, identification of genetic and dietary factors influencing fat levels in the blood and understanding how these factors interact will provide improved strategies for the prevention of heart disease. Several common genetic variants of the APOA5 gene, encoding a protein that participates in the transport of fat in the blood, were investigated for their role in promoting elevated levels of fat in the blood as well as suitability as indicators of future heart disease. We observed significant associations between genetic variants of ApoA5 and fat concentration in the blood of subjects in the Framingham Heart Study. Importantly, our studies indicate that two independent genetic variants exert differential risk on the likelihood of future heart disease. One such genetic variant is a strong indicator of increased risk for heart disease (and stroke). Overall, this study strongly suggests that genetic variants of ApoA5 contribute to the risk of heart disease likely by altering the function of the fat-carrying protein ApoA5, thereby raising fat levels in the blood, especially in men. We believe the findings of this research are of great interest to both the scientific community and the general public. This may lead ultimately to develop advanced strategies for the prevention and treatment of age-related disorders (e.g., heart disease, diabetes and obesity), and help us to achieve healthy aging through nutritional and behavioral approaches.

Technical Abstract: Apolipoprotein A5 (apoA-V) appears to play a relevant role in lipoprotein metabolism. The gene coding for apoA-V (APOA5) is located in chromosome 11 and several polymorphisms have been identified for which the minor allele has shown significant and consistent associations with increased triglyceride (TG) concentrations. However, the specific effects of these TG-raising alleles on lipoprotein metabolism and cardiovascular disease (CVD) risk has been less explored. We have investigated 5 single nucleotide polymorphisms (SNP) at the APOA5 locus in 1020 men and 1110 women participating in the Framingham Heart Study, and identified 3 major haplotypes representing 98% of all haplotypes at this locus. We found significant associations between APOA5 haplotypes and plasma TG, very low density lipoprotein (VLDL), high density lipoprotein cholesterol (HDL-C), remnant-like particles (RLP) concentrations, and low density lipoprotein (LDL) size distribution. We estimated the effects of these haplotypes on the variability of these lipid-related CVD risk predictors, providing a further understanding of the potential risk associated with the APOA5 locus. Our results show that common APOA5 variants contribute to CVD risk through their effects on triglyceride-rich lipoproteins, especially in men.