Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS).
One haplotype containing the minor alleles of the APOA5 (-1131T>C, c.553G>T) and APOA1 (-3013C>T,-75G>A) was more prevalent in cases than in controls (11.3% vs. 1.1%, respectively) and was statistically significantly associated with high triglycerides (adjusted odds ratio: 12.83, 95% confidence interval [CI]: 5.1-32.4, P<0.001).
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.
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.
The sequencing of the APOA5 gene in patients with primary hypertriglyceridemia, in whom mutations of the LPL and APOC2 genes had been excluded, led to the identification of four families with two different mutations in this gene predicted to result in truncated apolipoprotein A-V.
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).
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.
APOA5 Ala315>Val does not play any dominant/important role in the genetic determination of plasma TG levels, but the increased frequency in HTG patients compared to controls suggests that it might interact with other gene variants to cause HTG.