BACKGROUND/AIMS: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. METHODS: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). RESULTS: Total, LDL−, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL− and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. CONCLUSIONS: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.
Apolipoprotein A-I ; Apolipoprotein A-II ; Apolipoprotein C-II ; Apolipoprotein C-III ; Apolipoproteins ; Apolipoproteins B ; Apolipoproteins E ; Cholesterol ; Genotype ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Lipid Metabolism ; Lipoproteins ; Recurrence

BACKGROUND: Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. METHODS: We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. RESULTS: In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. CONCLUSIONS: Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.
Apolipoprotein A-II ; Area Under Curve ; Biomarkers ; Biomarkers, Tumor ; Carcinoembryonic Antigen ; Chemokine CCL5 ; Dataset ; Diagnosis ; Epididymis ; Humans ; Lung Neoplasms* ; Lung* ; Male ; Prealbumin ; Sensitivity and Specificity ; Vascular Cell Adhesion Molecule-1

BACKGROUND: Apolipoprotein A2 (APO A2) is the second most abundant structural apolipoprotein in high density lipoprotein. Several studies have examined the possible effect of APO A2 on atherosclerosis incidence. Due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between APO A2 -265T/C polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 180 T2DM patients, with known APO A2 -265T/C polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. Dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 [PTX3], high-sensitivity C-reactive protein [hs-CRP], and interleukin 18) were measured. The data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance. RESULTS: After adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the CC genotype showed higher hs-CRP (P=0.001, P=0.008, and P=0.01, respectively) and lower PTX3 (P=0.01, P=0.03, and P=0.04, respectively) in comparison with the T allele carriers. In the patients with the CC genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. However, regarding the T allele carriers, the plasma hs-CRP level was significantly higher in the obese patients compared to the non-obese patients (P=0.01). CONCLUSION: In the T2DM patients, the CC genotype could be considered as a risk factor and the T allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. Our results confirmed the anti-atherogenic effect of APO A2, though more studies are required to establish this effect.
Alleles ; Apolipoprotein A-II* ; Apolipoproteins ; Atherosclerosis ; C-Reactive Protein ; Diabetes Mellitus, Type 2* ; Genotype ; Humans ; Incidence ; Inflammation ; Interleukins ; Lipoproteins ; Obesity ; Plasma ; Risk Factors

Statins have been shown to be very effective and safe in numerous randomized clinical trials, and became the implacable first-line treatment against atherogenic dyslipidemia. However, even with optimal statin treatment, 60% to 80% of residual cardiovascular risk still exists. The patients with familial hypercholesterolemia which results in extremely high level of low density lipoprotein cholesterol (LDL-C) level and the patients who are intolerant or unresponsive to statins are the other hurdles of statin treatment. Recently, new classes of lipid-lowering drugs have been developed and some of them are available for the clinical practice. The pro-protein convertase subtilisin/kexintype 9 (PCSK9) inhibitor increases the expression of low density lipoprotein (LDL) receptor in hepatocytes by enhancing LDL receptor recycling. The microsomal triglyceride transport protein (MTP) inhibitor and antisense oligonucleotide against apolipoprotein B (ApoB) reduce the ApoB containing lipoprotein by blocking the hepatic very low density lipoprotein synthesis pathway. The apolipoprotein A1 (ApoA1) mimetics pursuing the beneficial effect of high density lipoprotein cholesterol and can reverse the course of atherosclerosis. ApoA1 mimetics had many controversial clinical data and need more validation in humans. The PCSK9 inhibitor recently showed promising results of significant LDL-C lowering in familial hypercholesterolemia (FH) patients from the long-term phase III trials. The MTP inhibitor and antisesnse oligonucleotide against ApoB were approved for the treatment of homozygous FH but still needs more consolidated evidences about hepatic safety such as hepatosteatosis. We would discuss the benefits and concerns of these new lipid-lowering drugs anticipating additional benefits beyond statin treatment.
Apolipoprotein A-I ; Apolipoproteins ; Apolipoproteins B ; Atherosclerosis ; Cholesterol, HDL ; Cholesterol, LDL ; Dyslipidemias* ; Hepatocytes ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Hyperlipoproteinemia Type II ; Lipoproteins ; Receptors, LDL ; Recycling ; Triglycerides

BACKGROUNDWilms' tumor (nephroblastoma) is a cancer of the kidneys that occurs typically in children and rarely in adults. Early diagnosis is very important for the treatment and prognosis of the disease. The aim of our study was to discover and identify potential non-invasive and convenient biomarkers for the diagnosis of Wilms' tumor.

METHODSNude mice were used to construct a Wilms' tumor model by injecting nephroblastoma cells into their bilateral abdomen. We collected 94 serum samples from mice consisting of 45 samples with Wilms' tumor and 49 controls. The serum proteomic profiles of the samples were analyzed via surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarkers were purified by high-performance liquid chromatography, identified by liquid chromatography-mass spectrometry, and validated using ProteinChip immunoassays.

RESULTSWe finally retrieved two differential proteins (m/z 4509.2; 6207.9), which were identified as apolipoprotein A-II and polyubiquitin, respectively. The expression of apolipoprotein A-II was higher in the Wilms' tumor group than in the control group (P < 0.01). By contrast, the expression of polyubiquitin was lower in the Wilms' tumor group than in the control group.

CONCLUSIONApolipoprotein A-II and polyubiquitin may be used as potential biomarkers for nephroblastoma in children, and the analysis of apolipoprotein A-II may help diagnose and treat Wilms' tumor.

Animals ; Apolipoprotein A-II ; blood ; Biomarkers ; blood ; Cell Line, Tumor ; Mice ; Mice, Nude ; Polyubiquitin ; blood ; Proteomics ; methods ; Wilms Tumor ; blood ; metabolism ; pathology

BACKGROUND: Apolipoprotein A-II (apoA-II) is the second-most abundant apolipoprotein in human high-density lipoprotein and its role in cardio metabolic risk is not entirely clear. It has been suggested to have poor anti-atherogenic or even pro-atherogenic properties, but there are few studies on the possible role of apoA-II in Asian populations. The aim of this study is to evaluate the role of apoA-II in metabolic syndrome (MetS) compared with apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) in Korean adults. METHODS: We analyzed data from 244 adults who visited the Center for Health Promotion in Pusan National University Yangsan Hospital for routine health examinations. RESULTS: The mean apoB level was significantly higher, and the mean apoA-I level was significantly lower, in MetS; however, there was no significant difference in apoA-II levels (30.5+/-4.6 mg/dL vs. 31.2+/-4.6 mg/dL, P=0.261). ApoA-II levels were more positively correlated with apoA-I levels than apoB levels. ApoA-II levels were less negatively correlated with homocysteine and high sensitivity C-reactive protein levels than apoA-I levels. The differences in MetS prevalence from the lowest to highest quartile of apoA-II were not significant (9.0%, 5.7%, 4.9%, and 6.6%, P=0.279). The relative risk of the highest quartile of apoA-II compared with the lowest quartile also was not significantly different (odds ratio, 0.96; 95% confidence interval, 0.95 to 1.04; P=0.956). CONCLUSION: Compared with apoA-I (negative association with MetS) and apoB (positive association with MetS) levels, apoA-II levels did not show any association with MetS in this study involving Korean adults. However, apoA-II may have both anti-atherogenic and pro-atherogenic properties.
Adult ; Apolipoprotein A-I ; Apolipoprotein A-II ; Apolipoproteins ; Apolipoproteins B ; Asian Continental Ancestry Group ; C-Reactive Protein ; Health Promotion ; Homocysteine ; Humans ; Lipoproteins ; Prevalence

OBJECTIVESTo screen differential proteins in serum from hepatocellular carcinoma (HCC) patients by Proteomic Technology and to purify and identify them.

METHODSSurface enhanced laser desorption Ionization time of flight-mass spectrum (SELDI-TOF-MS) was employed to screen differential proteins in serum from 33 HCC patients and 33 control cases, and then to purify and identify them using isoelectric precipitation, Tricine sodium dodecyl sulphate polyacrylamide gel electrophoresis (Tricine-SDS-PAGE) and high performance liquid chromatography tandem Mass Spectrum (HPLC-MS).

RESULTS65 protein peaks in the range of relative molecular weight from 2,000 to 10,000 were found significant difference (P less than 0.05) between the patient group and control group. Based on these differential protein peaks, diagnostic model for HCC detection was established and its sensitivity and specificity were 100% and 96.97% respectively. Proteins with 8,706.5 and 8,579.2 relative molecular weights (the t value was 2.562 and 2.783 respectively, and P value was 0.013 and 0.015 respectively) out of the 65 differential proteins were purified and identified, and then recognized as Apolipoprotein AII (Apo AII).

CONCLUSIONApo AII is probably a differential protein of HCC and maybe related to the pathogenesis of HCC.

Apolipoprotein A-II ; isolation & purification ; Blood Proteins ; analysis ; Carcinoma, Hepatocellular ; blood ; Case-Control Studies ; Humans ; Liver Neoplasms ; blood ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo seek the plasma differential proteins in patients with unstable angina of blood-stasis pattern (UA-BSS) for exploring the proteomic specialty in them by way of two-dimensional difference gel electrophoresis (DIGE) detection on plasma of patients and healthy persons.

METHODSUsing DIGE and tandem mass spectrometry, comparative proteomic study was conducted on the plasma of 12 UA patients of qi-deficiency and blood-stasis pattern (UA-QBS), 12 UA patients of phlegm-stasis cross-blocking pattern (UA-PSS) and 12 healthy volunteers.

RESULTSPreliminary results showed that Haptoglobin beta chain, DBP, HBB, HBA, Transthyretin, ApoA- I, ApoA-IV were significantly differentially expressed in both patterns, while Haptoglobin alpha1 chain, alpha-1-acid glycoprotein, ApoC-III, ApoA-II, ApoC-II, ApoJ, and Haptoglobin alpha 2 chain were only seen differentially expressed in the UA-PSS patients, alpha1-antitrypsin, Fibrinogen gamma chain, and Fibrin beta were only seen differentially expressed in UA-QBS patients.

CONCLUSIONThe common proteomics characteristics of patients of QBS and PSS patterns may be correlated with inflammatory reaction and metabolic disturbance (including blood lipid and blood oxygen).

Aged ; Angina, Unstable ; blood ; diagnosis ; Apolipoprotein A-II ; blood ; Apolipoprotein C-III ; blood ; Blood Proteins ; metabolism ; Case-Control Studies ; Female ; Fibrinogen ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Proteome ; analysis ; Proteomics ; Two-Dimensional Difference Gel Electrophoresis

OBJECTIVETo screen the mutations of the low density lipoprotein receptor (LDLR) gene in a familial hypercholesterolemia (FH) family, and analyze the LDL-uptaking function of LDLR on lymphocytes of patients.

METHODSGenomic DNA was extracted from four affected members in a Chinese FH family. The presence of apoB100 gene R3500Q mutation which results in familial defective apolipoprotein B100 (FDB) was excluded first. Fragments of the LDLR gene were amplified by touch-down polymerase chain reaction (Touch-down PCR) and analyzed by single-strand conformational polymorphism (SSCP). The suspect fragments of the LDLR gene were cloned and sequenced. Furthermore, the lymphocytes bounded with fluorescent-labeled LDL (DiI-LDL) were measured by fluorescence flow cytometry.

RESULTSA nonsense mutation was identified in exon 10 of LDLR gene. This mutation gave rise to a premature stop codon (W462X), resulting in the absence of most of the LDLR domains. It was detected in all the affected members of the FH family. The ratios of functional LDLR in lymphocytes from patients and normal controls were 63.7% and 77.3% respectively. As a result, the activity of the functional LDLR in patients was just 82.4% of that in the normal controls.

CONCLUSIONIt is possible that the W462X mutation of LDLR gene is the main cause for the disease in this family.

Adult ; Apolipoprotein B-100 ; genetics ; Base Sequence ; Case-Control Studies ; DNA Mutational Analysis ; Deoxyribonuclease I ; metabolism ; Exons ; genetics ; Female ; Flow Cytometry ; Humans ; Hyperlipoproteinemia Type II ; genetics ; metabolism ; pathology ; Lipoproteins, LDL ; metabolism ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Mutation ; Pedigree ; Receptors, LDL ; genetics ; metabolism

OBJECTIVETo investigate associations between the apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease (CAD).

METHODSapoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the polymorphisms of both apoCI and apoCII genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 203 cases of CAD and 365 controls. Pairwise linkage disequilibrium coefficients (D, D') were estimated by the LINKAGE program.

RESULTSThe frequencies of apoE E3/4 genotype (0.259) and epsilon4 (0.139) in CAD group were significantly higher than that in control group (0.125, 0.069), (P<0.05). The significant difference was also found for the apoCI locus, the frequencies of H2 allele were 0. 205 in the CAD and 0.113 in the control. Linkage disequilibrium coefficient D' was 0.672 (P<0.01) between apoE and apoCI genes. Significant differences for a deficit of epsilon3-H1-T1 and excess of epsilon4-H2-T1 were found in the CAD by estimation of the haplotype frequencies. After adjustment for possible confounding factors, the multivariate Logistic analysis showed a significant interaction among epsilon4, H2 and smoking, OR value was 18.3 (95%CI:2.35-150.81, P<0.05), attributable proportions of interaction (API) was 57.3%, it was a multiplicative model. An additive model was shown among epsilon4, H2 and bibulosity; the odds ratio (OR) (95%CI) and API of their interaction were 12.7(2.8-58.6, P<0.05) and 43.5%, respectively.

CONCLUSIONThe results suggested that both apoE and apoCI on chromosome 19 were the susceptibility loci for CAD, their linkage disequilibrium should be responsible for the development of CAD. Smoking and bibulosity can significantly increase the risk of CAD.

Aged ; Alcohol Drinking ; Apolipoprotein C-I ; genetics ; Apolipoprotein C-II ; genetics ; Apolipoproteins E ; genetics ; Coronary Artery Disease ; genetics ; Female ; Gene Frequency ; Haplotypes ; Humans ; Linkage Disequilibrium ; Logistic Models ; Male ; Middle Aged ; Multigene Family ; genetics ; Polymorphism, Genetic ; genetics ; Risk Factors ; Smoking