APOA5—a recent addition to genes determining plasma triglycerides

Abstract Raised plasma triglyceride (TG) levels is an independent risk factor for coronary artery disease (CAD), thus, understanding the genetic and environmental determinants of TG levels is of major importance. TG metabolism is a process for delivering free fatty acids for energy storage or β-oxidation, involving a number of different hydrolytic enzymes and apolipoproteins (apo). The genes encoding these proteins are, therefore, candidates for determining plasma TGs. There is evidence that common variations in LPL , apo CIII ( APOC3 ) and apo E ( APOE ) have the strong effect on plasma TG levels at the population level. More recently, the latest recognized member of the apolipoprotein gene family, APOA5 , identified by comparative sequencing between human and mouse DNA, was located approximately 27 kb distal to APOA4 in the APOA1 – C3 – A4 gene cluster on chromosome 11q23, and variation in APOA5 was shown to be associated with plasma TG levels. The involvement of variation in the APOA1 – C3 – A4 locus in determining differences in lipid levels is well documented. We have examined the relative influence of APOA5 variants on plasma lipids, compared to the impact of variation in other genes within the cluster to determine if these effects are independent or a consequence of the strong linkage disequilibrium across the locus.