|Lai, Chao Qiang|
Submitted to: Circulation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/23/2006
Publication Date: 5/2/2006
Citation: Lai, C., Corella, D., Demissie, S., Cupples, A., Adiconis, X., Zhu, Y., Ordovas, J.M. 2006. Dietary intake of n-6 fatty acids modulates effect of apolipoprotein a5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size: the framingham heart study. Circulation. 113(17):2062-70. Interpretive Summary: The feeding patterns of modern societies result in a situation by which most of the time humans are in the postprandial state. However, most blood markers associated with cardiovascular risk are measured in the fasting state. There is a dramatic variability in the way that individuals clear dietary fat from blood following food consumption and this may be associated with differential accumulation of potentially atherogenic lipoprotein particles known as lipoprotein remnants. Apolipoprotein A5 gene (APOA5) plays a key role in triglyceride (TG) transport and it may affect the clearance of remnant particles in the blood. Several polymorphisms have been identified in this gene and their minor alleles have been strongly associated with increased blood triglycerides and remnant lipoprotein levels in the blood. However, less is known about how these effects may be modulated by dietary fat. Polyunsaturated fatty acids (PUFA) have been known to lower blood cholesterol concentrations, but their benefit on cardiovascular risk may depend on their effects over other risk factors, such as remnant lipoproteins. We have investigated the interaction between the APOA5 gene and dietary fat in 1020 men and 1110 women in the Framingham Heart Study. We found that the TG-raising allele was associated with higher levels of remnant-like particles in the blood only when subjects where consuming 6% or more of total energy from PUFA. However, when PUFA consumption was less than 6%, there was no significant difference between the TG-raising allele carriers and the non-carriers. Our data demonstrate that diets high in PUFA may not decrease CVD risk on everybody, and particularly on those who carry variants alleles at the APOA5 gene.
Technical Abstract: Postprandial lipoprotein remnants have been shown to be independent atherogenic risk factors. Apolipoprotein A-V, encoded by the APOA5 gene plays a key role in triglyceride (TG) metabolism. Several polymorphisms have been identified, and their minor alleles have been shown to be strongly associated with increased TG levels. However, little is known about how APOA5 genetic variants modulate the effect of nutrients on lipid metabolism. We have investigated the interaction between APOA5 and dietary fat in 1020 men and 1110 women in the Framingham Study. We found a highly significant gene-diet interaction between APOA5 variants and PUFA intake. The minor APOA5 alleles were associated with higher TG and remnant-like particle (RLP-TG) concentrations only in subjects consuming >6% of total energy from PUFA fat (the mean intake of the population), particularly in men (p=0.0037 and p=0.0054). When PUFA consumption was less than 6%, there was no significant association between the minor alleles and plasma TG concentrations. Significant gene-PUFA interactions were found for VLDL and LDL sizes. However, we did not find significant interactions for total fat, saturated fat, and monounsaturated fat. In summary, high PUFA intake is associated with elevation in atherogenic lipoprotein fractions among those carrying specific minor alleles at the APOA5 locus, which potentially may result in increased CVD risk.