Apolipoprotein A5 (Apo A5) is a novel member in apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.
Apolipoprotein A-V ; genetics ; Atherosclerosis ; genetics ; Gene Frequency ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Triglycerides ; metabolism

OBJECTIVETo investigate the association between the -1131T/C and 56C/G polymorphism in the APOA5 gene as well as the -482C/T in the APOC3 gene and susceptibility to coronary artery disease (CAD) in a Chinese Han population.

METHODSUsing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE) methods, we analyzed the genotypes in 312 CAD patients diagnosed by angiography and 317 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods.

RESULTSThe frequency of the APOA5 -1131 C allele in CAD patients was significantly higher than that of the control group (39.9% vs. 33.3%, P = 0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR = 1.93 and OR = 1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P < 0.01).

CONCLUSIONSThe APOA5-1131T/C polymorphism but not APOC3-482C/T might contribute to an increased risk of CAD among Chinese accompanied by an elevation of serum TG levels; this effect was found to be independent of the APOC3-482C/T variant.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Apolipoprotein A-V ; Apolipoprotein C-III ; genetics ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; Coronary Artery Disease ; blood ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Triglycerides ; blood

We investigated the prevalence and characteristics of variants of five lipolysis-related genes in Korean patients with very high triglycerides (TGs). Twenty-six patients with TG levels >885 mg/dL were selected from 13545 Korean subjects. Five candidate genes, LPL, APOC2, GPIHBP1, APOA5, and LMF1, were sequenced by targeted next-generation sequencing. Predictions of functional effects were performed and matched against public databases of variants. Ten rare variants of three genes were found in nine (34.6%) patients (three in LPL, four in APOA5, and three in LMF1). Five were novel and all variants were suspected of being disease-causing. Nine were heterozygous, and one (3.8%) had a homozygous rare variant of LPL. Six common variants of four genes were observed in 25 (96.2%) patients (one in LPL, one in GPIHBP1, two in APOA5, and two in LMF1). The c.G41T variant of GPIHBP1 and c.G533T variant of APOA5 were most frequent and found in 15 (57.7%) and 14 (53.8%) patients, respectively. Rare homozygous variants of the genes were very uncommon, while diverse rare heterozygous variants were commonly identified. Taken together, most study subjects may be manifesting the combined effects of rare heterozygous variants and common variants.
Apolipoprotein A-V ; Asian Continental Ancestry Group/genetics ; Female ; Genetic Association Studies ; Genetic Variation ; Heterozygote ; Humans ; Lipolysis/genetics ; Male ; Middle Aged ; Triglycerides/blood

OBJECTIVETo investigate the relationship between apolipoprotein A5(apoA5) - 1131T > C polymorphism and the susceptibility of coronary artery disease (CAD) in Chinese.

METHODSThe restriction fragment length polymorphism of apoA5 gene - 1131T > C was studied using PCR in a case-control study which enrolled 235 patients with CAD diagnosed by angiography and 262 healthy controls from Jiangsu province.

RESULTSThe frequencies of T, C allele were 59.57%ì40.43% and 65.65%, 34.35% in CAD group and control group respectively. There was statistically significant difference in allele frequencies between CAD group and control group (P < 0.05). The susceptibility to CAD for the CC genotype was much higher than that for wild type TT (OR = 1.872, 95% CI = 1.039 - 3.376, P = 0.037), even after the use of Logistic regression models (OR = 2.285, 95% CI = 1.222 - 4.274, P = 0.012). In control group, there was significant difference in TG levels among different genotypes, the C allele carriers had higher serum TG concentration (P = 0.007).

CONCLUSIONapoA5 - 1131T > C polymorphism is associated with an increased risk of CAD and is also in strong association with serum TG levels.

Aged ; Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; Coronary Artery Disease ; blood ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Humans ; Lipids ; blood ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Triglycerides ; blood

OBJECTIVETo investigate the association of the -12238T/C polymorphism of apolipoprotein A5 (APOA5) gene with coronary heart disease (CHD) and the influence of serum lipid levels in Chinese Uygur population of Xinjiang.

METHODSThe -12238T/C polymorphism of APOA5 gene in 344 patients with CHD and 408 controls was analyzed by polymerase chain reaction-restriction fragment length polymorphism; the serum lipid levels were detected as well.

RESULTSThe frequencies of CC, TC and TT genotype were 6.69%, 43.31% and 50.00% in the CHD group, while they were 14.95%, 45.10% and 39.95% in the control group. There was significant difference in the distribution of genotypes between the two groups (P < 0.01). Logistic regression analyses adjusted for age, gender, smoking, serum total cholesterol, presence of hypertension and diabetes revealed that individuals carrying CC genotype had an increased risk of CHD compared with TT genotype (OR = 0.328, 95%CI: 0.154-0.700). There was also significant difference in serum triglyceride level in genotypes between these two groups (P < 0.01). Patients in CHD group who carried CC and TC genotypes had lower serum triglyceride level than the TT genotype carriers.

CONCLUSIONThe -12238T/C polymorphism of APOA5 gene has influence on the serum triglyceride level in Uygur population of Xinjianxg. This polymorphism might be associated with development of CHD, and the CC genotype might be a protective factor in the development of CHD.

Adult ; Aged ; Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Coronary Disease ; blood ; ethnology ; genetics ; Ethnic Groups ; genetics ; Female ; Genotype ; Humans ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic ; Triglycerides ; blood

OBJECTIVETo investigate the single nucleotide polymorphism 4 (SNP4) of the apolipoprotein A5 (APOA5) gene possible association with coronary heart disease(CHD) and its distribution of in Chinese Han population.

METHODSAPOA5 SNP4 genotyping was performed using polymerase chain reaction and Hae III restriction fragment length polymorphism analysis.

RESULTSAPOA5 allelic frequencies of T, C were 0.435, 0.565 and 0.374, 0.626 in CHD group and control group, respectively. There is significant difference in allele and genotype frequencies between CHD group and control group (P<0.05). The levels of plasma high density lipoprotein in CHD patients with CC genotype were higher than those in CHD patients with other genotypes (P<0.01). The frequencies of T allele and C allele in Chinese was significantly different from those in Caucasians (0.374 vs 0.663, 0.626 vs 0.337, P<0.01). The C allele was much more common in Chinese population.

CONCLUSIONThe association is found between the Hae III polymorphism and CHD, There is a significant correlation between the CC genotype of the APOA5 and the levels of plasma high density lipoprotein-cholosteal in the CHD group.

Adult ; Aged ; Aged, 80 and over ; Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; Coronary Disease ; blood ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVETo explore the relationship between the expression characteristics of lipid metabolism-related genes in the liver and early atherosclerotic lesions in apolipoprotein E and low density lipoprotein receptor gene double knockout (apoE(-/-)/LDLR(-/-)) mice.

METHODSRT-PCR was used to detect the differential expression of lipid metabolism-related genes in the liver of apoE(-/-)/LDLR(-/-) and wild type (WT) mice. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) level as well as aortic morphology were also analyzed.

RESULTSAmong the 11 lipid metabolism-related genes, apolipoprotein B100 (apoB100) mRNA levels were significantly higher in apoE(-/-)/LDLR(-/-)mice compared with WT mice. At 14 days, 1, 2 and 3 months of age, the level of mRNA expression were 1.55, 1.47, 1.50 and 2.42 folds of those of the age matched WT mice respectively. The fatty acid transporter (FAT/CD36) mRNA expression levels were higher in 14-day and 3-month old mice at 1.30 and 1.35 folds of those of the age matched WT mice, respectively. Apolipoprotein A IV (apoA IV) and Apolipoprotein AV (apoAV) mRNA levels were significantly down-regulated (0.89 fold decrease in 14-day, and 0.90 folds decrease in 3-month, respectively). The mRNA expression levels of apolipoprotein AI (apo AI), apolipoprotein F (apo F), peroxidase proliferator-activated receptor alpha (PPAR-alpha), liver X receptor alpha (LXRalpha), angiopoietin-like protein 3 (ANGPTL3), acyl-coenzymeA oxidase 1 (ACOX1) and carnitine palmitoyl transferase 1 (CPT1) had no significant changes. Serum TC, TG and LDL-C were higher than those of age matched WT mice at 7, 2 and 30 folds, respectively. Furthermore, apoE(-/-)/LDLR(-/-) mice demonstrated typical early atherosclerotic lesions at sinus and root regions of aorta in an age dependent manner.

CONCLUSIONAlterations of the expression of lipid metabolism-related genes in liver play important roles in the development of AS in the apoE(-/-)/LDLR(-/-) mice at early ages.

Animals ; Aorta ; pathology ; Apolipoprotein A-V ; Apolipoprotein B-100 ; biosynthesis ; genetics ; Apolipoproteins ; biosynthesis ; genetics ; Apolipoproteins A ; biosynthesis ; genetics ; Apolipoproteins E ; deficiency ; Atherosclerosis ; etiology ; metabolism ; pathology ; CD36 Antigens ; biosynthesis ; genetics ; Gene Expression ; Lipid Metabolism ; Liver ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Messenger ; metabolism ; Receptors, LDL ; deficiency

OBJECTIVES: Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD. METHODS: This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. RESULTS: After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced. CONCLUSIONS The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.
Animals ; Apolipoprotein A-V/genetics* ; Body Weight ; Dimethyl Sulfoxide/metabolism* ; Liver/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/chemically induced* ; Olanzapine/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering ; Triglycerides

OBJECTIVETo investigate the relationship between the polymorphism of apolipoprotein A5 gene (APOA5) -12238 T>C and atherosclerotic cerebral infarction (ACI).

METHODSThree hundred and forty-one subjects (170 ACI patients and 171 healthy controls) were collected to determine the genotypes by using polymerase chain reaction-restriction fragment length polymorphisms.

RESULTSAPOA5 allele frequencies of T/C were 0.588/0.412 and 0.424/0.576 in ACI group and control group respectively. There was significant difference in allele and genotype frequencies between ACI group and control group (P < 0.05). The levels of plasma triglyceride in ACI patients with TT genotype were higher than those in patients with CC genotypes (P < 0.05).

CONCLUSIONThe relationship is found between the site of APOA5 gene -12238 T>C and ACI. There is a significant correlation between TT genotype of APOA5 and the levels of plasma triglyceride in patients with ACI.

Apolipoprotein A-V ; Apolipoproteins A ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Cerebral Infarction ; blood ; complications ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Intracranial Arteriosclerosis ; blood ; complications ; genetics ; Lipids ; blood ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length