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The protein encoded by this gene is an apolipoprotein and an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. This gene uses alternate polyadenylation sites and is located proximal to the apolipoprotein gene cluster on chromosome 11q23. A novel genetic variant in APOA5 is associated with hypertriglyceridemia. A strong association suggested between T-113C polymorphism in the APOA-V gene and the levels of plasma triglycerides. APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner. APOA5 gene expression is regulated by the LXR ligand T0901317 in a negative manner through SREBP-1c. APOA5 gene is involved in hypertriglyceridemia associated with hyperinsulinemia. APOA5 is a highly responsive peroxisome proliferator-activated receptor alpha target gene with a role as a major mediator for how fibrates reduce plasma triglycerides in humans. APOA5 plays a role in the ethnic differences observed for plasma TG and HDL cholesterol concentrations. APOa5 may have a role in predisposition to cardiovascular disease. ApoA-V regulates the secretion and/or catabolism of triglyceride-rich lipoproteins. A nonsense mutation in APOA5 gene (Q145X) was found in a boy with hyperchylomicronemia syndrome. This is the first observation of a complete apoA-V deficiency in humans. ApoAIV is a direct target gene of Liver X receptors (LXRs) that may contribute to the antiatherogenic effect of LXR activation. ApoAV is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate RORalpha transactivation. Polymorphism in the apoAV gene influences serum TG in populations of different ethnicities. Review. APOA5 represents a newly discovered gene involved in triglyceride metabolism in both humans and mice whose mechanism of action remains to be deciphered. S19W and -1131T>C variations in APOA5 gene are associated with and appear to be genetic risk factors for coronary heart disease susceptibility in Chinese. TriglycerideS were significantly higher and HDL cholesterol was decreased in -1131C carriers. There is a strong association between the Ser19 to Trp substitution polymorphism in the APOAV gene and extreme concentrations of plasma triglycerides in hypertriglyceridemic patients. Two haplotypes are found in 25-50% of subjects, supporting the contribution of common variation to quantitative phenotypes. Val153-Met polymorphism in the APOAV gene does not represent an important risk factor for developing the extreme levels of plasma triglycerides. Variation in APOA5 is associated with differences in triglycerides in healthy men. A major genetic determinant of both LDL particle size and plasma TG levels among ethnic Japanese - data confirm interrelationships that determine CHD risk factors and CHD itself. An important determinant of plasma triglyceride levels. ApoA-V lipid complexes bind heparin and, when present on triglyceride-rich lipoprotein particles, may promote their association with cell surface heparan sulfate proteoglycans. ApoA-V may function intracellularly to modulate hepatic VLDL synthesis and/or secretion. Examination of overexpression on decreased plasma triglyceride levels. No association between APOA5 gene polymorphisms or haplotypes and coronary artery disease as determined by angiography. Relationship of APOA5 -1131T>C and S19W with lipid subfractions and progression of atherosclerosis. The apoCIII enhancer regulates expression of apoAI, apo-CIII, and apoAIV but not apoAV in vivo; the entire cluster has roles in regulating lipid metabolism.
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