The Novel Apolipoprotein A5 Is Present in Human Serum, Is Associated with VLDL, HDL, and Chylomicrons, and Circulates at Very Low Concentrations Compared with Other Apolipoproteins

O’Brien, Peter J.; Alborn, William E.; Sloan, John H.; Ulmer, Maverick; Boodhoo, Amechand; Knierman, Michael D.; Schultze, A. Eric; Konrad, Robert J.

doi:10.1373/clinchem.2004.040824

Cited by 182 publications

(172 citation statements)

References 28 publications

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“…In contrast, all VLDL particles are carrying one or more APOC3 molecules. Average plasma APOA5 levels have been reported in healthy normolipidaemic volunteers of Caucasian origin as 16 μg/100 ml [19] and 1 μg/100 ml [22], and in healthy Japanese subjects as 18 μg/100 ml [17]. In our patients with type 2 diabetes, who were of Caucasian origin and had moderately elevated plasma triglyceride levels, plasma APOA5 levels were 7 to 139 μg/100 ml.…”

Section: Discussionmentioning

confidence: 48%

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Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

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Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in patients with type 2 diabetes at baseline and during atorvastatin treatment, a lipid-lowering treatment that results in a reduction in plasma triglycerides and APOC3. Subjects, materials and methods: Plasma APOA5 concentration was measured by ELISA in 215 subjects with type 2 diabetes, who were taken from the Diabetes Atorvastatin Lipid-lowering Intervention (DALI) study, a 30-week randomised, double-blind, placebo-controlled study, and given atorvastatin 10 mg or 80 mg daily. Results: At baseline, average plasma APOA5 concentration was 25.7±15.6 μg/100 ml. Plasma APOA5 (R s =0.40), APOC3 (R s =0.72) and APOE (R s =0.45) were positively correlated with plasma triglyceride levels (all p<0.001). In multiple linear regression analysis, adjusted for age and sex, the variation in plasma triglycerides was explained mostly by APOC3 (52%) and only to a small extent by APOA5 (6%) and APOE (1%). Atorvastatin treatment decreased plasma triglycerides, APOA5, APOC3 and APOE (all p<0.0001). After treatment, APOC3 remained the major determinant of plasma triglyceride levels (59%), while the contributions of APOA5 and APOE were insignificant (2 and 3%). Conclusions/interpretation: Our findings reveal a positive association between plasma APOA5 and triglycerides in patients with type 2 diabetes. Treatment with atorvastatin decreased plasma APOA5, APOC3, APOE and triglycerides. In contrast to APOC3, APOA5 is not a major determinant of triglyceride metabolism in these patients.

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Section: Discussionmentioning

confidence: 48%

“…The recent development of specific immunoassays for human APOA5 enables in-depth investigation of the role of APOA5 in human lipoprotein metabolism. APOA5 in human plasma is present on VLDL and HDL particles [19]. However, its total plasma concentration is very low and only about 4% of VLDL particles carry an APOA5 molecule [20,21].…”

Section: Discussionmentioning

confidence: 99%

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

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“…Previous studies have shown that several polymorphisms in or near APOA5 are significantly associated with serum triglycerides concentrations (23)(24)(25)(26). rs964184 of ZPR1 has been associated with serum triglycerides and this may be attributable to linkage disequilibrium with functional SNPs in APOA5, which influence metabolism of chylomicrons, very-low-density lipoprotein and HDL (27). As an increase in serum triglycerides concentration is an important risk factor for type 2 DM (28), a multivariable logistic regression analysis was performed with adjustment for serum triglycerides levels or hypertriglyceridemia in addition to age, gender and BMI.…”

Section: Discussionmentioning

confidence: 99%

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

et al. 2014

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Abstract.Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ≤0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the χ 2 test revealed that the rs964184 (C→G) of the ZPR1 zinc finger gene (ZPR1) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 was significantly associated (P= 0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.

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“…Single nucleotide polymorphisms (SNPs) in the APOA5 gene (11q23) were found to be strongly associated with plasma TG levels. 21,22 Data from family studies on type III HLP indicate that one or more genes are possible additional genetic factors predisposing to type III HLP. 4 However, from these studies it was not evident which additional genes were involved or whether the study population was very small.…”

Section: Introductionmentioning

confidence: 99%

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

et al. 2008

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Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper-and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G4C and APOA5 À1131 T4C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (Po0.05). Furthermore, the frequencies of the APOA5 c.56 G4C polymorphism and LPL c.27 G4A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 À1131 T4C, c.56 G4C and/or LPL c.27 G4A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval ¼ 1.8 -7.5, Po0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G4C/APOA5 À1131 T4C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.

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The Novel Apolipoprotein A5 Is Present in Human Serum, Is Associated with VLDL, HDL, and Chylomicrons, and Circulates at Very Low Concentrations Compared with Other Apolipoproteins

Cited by 182 publications

References 28 publications

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Association of a genetic variant of the ZPR1 zinc finger gene with type 2 diabetes mellitus

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

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