Recent findings indicate that APOA5 could also influence cholesterol homeostasis and probably play a role in hypertriglyceridemia associated with diabetes and inflammation.
Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS).
Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an increased risk of myocardial infarction (MI).
Various studies have identified a number of common (APOA5 c.56C>G; p.S19W; rs 3135506 ) and rare variants in the APOA5 gene in individuals with hypertriglyceridemia.
In multivariate logistic regression analyses the odds ratio (OR [95% Cl]) of hypertriglyceridemia (3rd vs. 1st tertile of triglyceride distribution) was 3.60 [1.38-9.42] in control subjects bearing at least one APOA5 19W variant.
ApoA5 loss-of-function single nucleotide polymorphisms are associated with reduced lipolysis, poor remnant clearance and concomitantly, hypertriglyceridemia.
Compared with APOA5 c.553 GG carriers, c.553T carriers displayed an increased risk of HTG in the Asian population, with an overall random effects OR of 3.55 (95% CI: 2.46-5.13) in the dominant model.
To examine the genetic variants of 3 candidate genes known to influence triglyceride metabolism, LPL, APOC2, and APOA5, which encode lipoprotein lipase, apolipoprotein C-II, and apolipoprotein A-V, respectively, in a large group of Thai subjects with severe hypertriglyceridemia.
We investigated whether apoA-V complexed with phospholipid in the form of a reconstituted high-density lipoprotein (rHDL) has potential utility as a therapeutic agent for treatment of hypertriglyceridemia (HTG) when delivered intravenously.
The apolipoprotein A5 gene (APOA5) -1131 T > C polymorphism is associated with mild hypertriglyceridemia in type 2 diabetic subjects, and interacts with dietary fat in the determination of triglyceride concentrations.
Variants in the lipoprotein lipase (LPL), apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), GPIHBP1 and LMF1 genes may cause severe hypertriglyceridemia (HTG), which is now the second-leading aetiology of acute pancreatitis in China.
Another child was found to be homozygous for a nonsense variant of APOA5, which was also found in homozygous state in his father with longstanding HyperTG.
To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis.
Receipt of protease inhibitor-based HAART, high baseline triglyceride levels, and carriage of APOA5 SNP3 or c.553G>T variants or APOA5 SNP1T/SNP2G/SNP3C/c.553T haplotype were statistically significantly associated with development of extreme hypertriglyceridemia (triglyceride level, >500 mg/dL).
Approach and Results- Here, we reconstitute the environment-induced hypertriglyceridemia phenotype of human APOA5 deficiency in Apoa5<sup>-/-</sup> mice and delineate the role of SREBP-1c in vivo by generating Apoa5<sup>-/-</sup> ;Srebp-1c<sup>-/-</sup> mice.
The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk.
Only APOA5 c.553 G ＞ T (rs2075291), resulting in the amino acid mutation rs2075291" genes_norm="116519">Gly185Cys, co-segregated well with hypertriglyceridemia in terms of autosomal recessive inheritance (homozygote TT: mean triglyceride level: 1,071 mg/dL vs non TT (GT and GG): mean triglyceride level: 118 mg/dL; p ＜ 0.001) in the index family.
These results indicate that polymorphisms of APOA5, APOC3, APOA1, and LPL are determinants of hypertriglyceridemia and that those of APOA5 and APOE are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively, in Japanese individuals.