ABSTRACT
BACKGROUND: The apolipoprotein A5 gene (ApoA5) plays an important role in modulating triglyceride metabolism. Polymorphisms of ApoA5, including -1131T>C and c.553G>T (G185C), have been reported to correlate with hypertriglyceridemia (HTG). In the present study the relationships of 5 single nucleotide polymorphisms, including the -1131T>C, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C polymorphisms of ApoA5, with HTG were investigated. METHODS AND RESULTS: The study group comprised 95 Japanese patients with HTG and 119 unrelated normolipidemic subjects. Frequencies of the C allele of -1131T>C (0.511) and the T allele of c.553G>T (0.205) in the hypertriglyceridemic patients were significantly higher than in the normolipidemic subjects (0.315 and 0.105, respectively). The c.56C>G (S19W) polymorphism was not observed, and the other 4 polymorphic sites were in strong linkage disequilibrium. Five of the 8 detected haplotypes with the C allele of -1131T>C correlated with HTG. Promoter activities of ApoA5, including that with the -1131T>C polymorphism, were estimated using a luciferase assay. Analysis of ApoA5 promoters showed that the -1131T>C polymorphism alone had no effect. Comparison of expression of mutant G185C and wild-type ApoA5-green fluorescent protein (GFP) in HepG2 cells showed that ApoA5-GFP was abundant in punctate endosome-like structures, and ApoA5 (G185C)-GFP expression resembled that of the wild type. CONCLUSIONS: The -1131T>C and c.553G>T (G185C) polymorphisms correlated with HTG in this Japanese population, but neither polymorphism directly affected ApoA5 expression.
Subject(s)
Apolipoproteins A/genetics , Asian People/genetics , Hypertriglyceridemia/genetics , Linkage Disequilibrium , Polymorphism, Genetic , Aged , Apolipoprotein A-V , Apolipoproteins A/metabolism , Base Sequence , Cell Line, Tumor , Cytosine , Female , Gene Frequency , Guanine , Haplotypes , Humans , Hypertriglyceridemia/metabolism , Male , Middle Aged , Promoter Regions, Genetic , Thymine , Tissue DistributionABSTRACT
BACKGROUND: The present study examined the effects of atorvastatin and the in vitro effect of apolipoprotein (apo) A-I/phosphatidylcholine (POPC) discs on charge-based triglyceride-rich lipoprotein (TRL) subfractions in a patient with type III hyperlipoproteinemia (HLP) and the apoE2/2 phenotype. METHODS: Charge-based lipoprotein subfractions were characterized by capillary isotachophoresis (cITP). cITP analysis was performed using plasma that had been prestained with a lipophilic dye on a Beckman P/ACE MDQ system. RESULTS: Treatment with atorvastatin for 4 weeks markedly decreased the slow (s)-migrating TRL subfraction and both fast- and slow-migrating low-density lipoprotein (LDL) subfractions, but did not affect the fast (f)-migrating TRL subfraction in this patient. ApoA-I/POPC discs consisted of two major charge-based subfractions that had the mobility of cITP fTRL and sTRL. Incubation of plasma from this patient in the presence of apoA-I/POPC discs caused not only a reduction in cITP fast- and intermediate-migrating HDL and an increase in cITP sHDL but also a reduction in fTRL and sTRL and an increase in sLDL. CONCLUSION: Atorvastatin and apoA-I/POPC discs decreased cITP TRL subfractions in a complementary manner, suggesting that the combination of apoA-I/POPC discs and atorvastatin could be a promising therapeutic approach for hypertriglyceridemia.
