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: Hypertriglyceridemia (HTG) has been considered a characteristic plasma lipid abnormality in hemodialysis patients with chronic renal failure, but is actually shown in only some of them (30-50%). Also renal dyslipidemia may contribute to atherosclerosis in hemodialysis patients. METHODS: Study population consisted of 34 patients with normotriglyceridemia (NTG), 11 patients with HTG and 47 controls. We measured total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein (apo) A-I, apoB, apoC-III and apoE. RESULTS: Compared with controls, the NTG patients had significantly decreased levels of TC, HDL-C, and low density lipoprotein-cholesterol (LDL-C). But HTG patients had significantly increased TG, and TC/HDL-C ratio which were considered to represent the atherogenic indicator and had decreased HDL-C and LDL-C (P <0.001), with significant increase of TG and TC/HDL-C ratio compared with those of NTG patients. In the apolipoprotein profiles, all patients showed decreased levels of apoA-I, apoB, and apoA-I/apoC-III ratio and increased levels of apoC-III and apoC-III/apoE ratio compared with those of controls (P <0.001). Especially, HTG patients had significantly increased levels of apoC-III compared with NTG patients. CONCLUSIONS: So these results indicated that abnormalities of those potentially atherogenic lipid and lipoproteins may contribute to the high incidence of cardiovascular diseases and progression of renal disease in the HTG patients than NTG patients on maintenance hemodialysis.
Apolipoprotein A-I ; Apolipoprotein C-III ; Apolipoproteins B ; Apolipoproteins E ; Apolipoproteins* ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol ; Dyslipidemias ; Humans ; Hypertriglyceridemia ; Incidence ; Kidney Failure, Chronic* ; Lipoproteins* ; Plasma ; Renal Dialysis* ; Triglycerides

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

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

We prepared two monoclonal antibodies-A-I30 and A-I4 to HDL apo A-I-with the ultimate goals of expressing and overproducing the valuable immunodiagnostic single chain Fv by phage display libraries in E, coli. Monoclonal antibodies were produced by immunizing mice with apolipoprotein A-I, and purified from ascitic fluid by affinity chromatography on a Protein A Sepharose CL-4B column. The specificity of A-I30 and A-I4 was confirmed by ELISA and Western blotting. The dissociation constants(Kd) of antigen-antibody complex obtained by enzyme linked immunosorbent assay(ELISA) method were 2.25 x 10(-8) M for A-I30 and 2.15 x 10(-8) M for A-I4. The experimental values of Kd are shown to be close to those obtained by immunoprecipitation of the radiolabeled antigen. From the above results, it was shown that A-I30 and A-I4 could be provided as excellent reagents for the determination of plasma HDL concentrations in clinical specimens using ELISA.
Animal ; Antibodies, Monoclonal/*immunology/isolation & purification ; Antibody Affinity ; Apolipoprotein A-I/*immunology ; Blotting, Western ; Hybridomas ; Lipoproteins, HDL/immunology ; Mice ; Mice, Inbred BALB C ; Tumor Cells, Cultured

BACKGROUND: Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.
Albuminuria ; Apolipoprotein A-I ; Atherosclerosis ; C-Reactive Protein ; Calcium ; Cardiovascular Diseases ; Cause of Death ; Coronary Artery Disease ; Coronary Vessels ; Creatinine ; Diabetes Mellitus, Type 2 ; Humans ; Risk Factors

BACKGROUND: Alterations of lipid profiles are well known in thyroid dysfunction. Hypothyroidism is associated with premature atherosclerosis. This relation has been attributed to increased levels of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B. However, there have been dissenting reports of abnormalities in serum lipid concentrations in patients with subclinical hypothyroidism. Serum Lp(a), an independent risk factor of atherosclerosis, is predicted according to thyroid function status. C-reactive protein (CRP) is very sensitive acute phase reactant and independently associated with the occurrence of atherosclerosis. Overt hypothyroidism is a cause of atherosclerosis, so it is expected that serum level of CRP may be related with thyroid dysfunction. However, no study has been performed about it. The objective of the study was to evaluate the relation of plasma CRP, apo A1, apo B and Lp(a) with thyroid function. METHODS: We undertook this study in 54 patients with hyperthyroidism, 35 patients with subclinical hyperthyroidism, 29 patients with overt hypothyroidism, 194 patients with subclinical hypothyroidism and 100 age and sex matched healthy control subjects. Serum CRP and Lp(a) were measured by immuno-nephelometry. RESULTS: There were no significant differences of serum CRP, Lp(a), HDL-C and apo A1 according to thyroid dysfunction. Serum total cholesterol level was lower in hyperthyroidism than in overt hyperthyroidism, subclinical hypothyroidism, subclinical hyperthyroidism and healthy control subjects (p<0.05). Serum LDL-C level was lower in hyperthyroidism than overt hypothyroidism (p<0.05). Serum triglyceride level was higher in overt hypothyroidism than in hyperthyroidism and healthy control subjects (p<0.05). Serum apo B level was lower in hyperthyroidism than in overt hyperthyroidism, subclinical hypothyroidism and healthy control subjects (p<0.05). CONCLUSION: Serum CRP and Lp(a), risk factors of atherosclerosis, were not significantly different according to thyroid dysfunction. Increased risk for atherosclerosis in overt hypothyroidism seems not to be associated with serum CRP level.
Apolipoprotein A-I* ; Apolipoproteins B ; Apolipoproteins* ; Atherosclerosis ; C-Reactive Protein ; Cholesterol ; Cholesterol, LDL ; Dissent and Disputes ; Humans ; Hyperthyroidism ; Hypothyroidism ; Plasma* ; Risk Factors ; Thyroid Gland* ; Triglycerides

BACKGROUND: Subjects with growth hormone-deficiency (GHD) have increased cardiovascular mortality, and growth hormone (GH) replacement may modulate cardiovascular disease risk. Therefore, we evaluated the effects of GH administration on the markers of cardiovascular disease in subjects with GHD. METHODS: 37 subjects (12 men and 25 women) with GHD and 65 normal subjects were enrolled in this study. GH or placebo were given for 3 months at a dose adjusted for normal serum insulin-like growth factor-I (IGF-I) level. Height, weight, waist circumference, hip circumference, lean body mass, fat mass, blood pressure, fasting blood glucose, IGF-I, lipid profile, uric acid, C-reactive protein (CRP), plaminogen activator inhibitor-1 (PAI-1), apolipoprotein AI, and quality of life-assessment of growth hormone deficiency in adults (QoL-AGHDA) were measured at baseline and month 3. RESULTS: Subjects with GHD showed higher levels of triglyceride, CRP, and PAI-1, but lower level of fasting glucose than normal subjects. Fat mass, CRP, and PAI-1 levels decreased in GH recipients (fat mass; 21.9+/-6.6 to 21.3+/-6.7%, p<0.05, CRP; 2.73+/-2.11 to 1.47+/-1.29 mg/L, p<0.001, PAI-1; 48.9+/-33.2 to 31.6+/-28.5 ng/mL, p<0.05). Fasting blood glucose and total cholesterol levels increased in GH recipients (fasting blood glucose; 4.58+/-0.46 to 4.81+/-0.36 mmol/L, p<0.05, total cholesterol; 5.36+/-1.31 to 6.17+/-1.12 mmol/L, p<0.01). Placebo recipients showed decrease in waist-hip ratio (0.93+/-0.05 to 0.92+/-0.04, p<0.05) and increase in fasting blood glucsoe (4.63+/-0.38 to 4.89+/-0.45 mmol/L, p<0.05) and uric acid (319.6+/-89.2 to 335.6+/-89.2 micro mol/L, p<0.05). QoL-AGHDA score improved in both groups (GH recipients; 10.0+/-6.0 to 7.4+/-5.5, p<0.01, placebo recipients; 9.8+/-4.4 to 6.7+/-3.4, p<0.05). CONCLUSION: Our results demonstrated favourable effects of GH on cardiovascular disease through modulating CRP and PAI-1 plasma level in subjects with GHD.
Adult* ; Apolipoprotein A-I ; Blood Glucose ; Blood Pressure ; C-Reactive Protein ; Cardiovascular Diseases* ; Cholesterol ; Fasting ; Glucose ; Growth Hormone* ; Hip ; Humans ; Insulin-Like Growth Factor I ; Male ; Mortality ; Plasma ; Plasminogen Activator Inhibitor 1 ; Triglycerides ; Uric Acid ; Waist Circumference ; Waist-Hip Ratio

BACKGROUND AND OBJECTIVES: The relationship between short-term hypothyroidism due to levothyroxine (LT4) withdrawal for radioactive iodine (RI) therapy in patients with differentiated thyroid cancer (DTC) and risk of cardiovascular disease is not clear. In this study, we evaluated the impact of short-term overt hypothyroidism on lipid profiles and cardiovascular parameters in patients with DTC. MATERIALS AND METHODS: We recruited 195 patients with DTC who were preparing RI therapy from March 2008 to February 2012. We analyzed the effect of thyroid stimulating hormone (TSH) level on the clinical, biochemical, and cardiovascular risk markers at the end of LT4 withdrawal protocol (P2). RESULTS: After LT4 withdrawal (P2), TSH and total cholesterol (TC) levels were significantly increased (p<0.005). After adjustment for multiple factors such as age, sex, body mass index (BMI), hypertension and diabetes mellitus (DM), the positive relationship between TSH and TC remained significant (p=0.04). Mean levels of homocysteine, low density lipoprotein-cholesterol, triglyceride were increased. However, levels of high density lipoprotein-cholesterol, cystatin C, C-reactive protein, apolipoprotein B (ApoB), apolipoprotein A1 (Apo A1), lipoprotein (a) (Lp[a]), aspartate transaminase, alanine aminotransferase, total bilirubin, uric acid remained within normal range. Splitting the whole cohort into the three different age groups, serum Apo B, Lp(a) levels and BMI increased with increasing age (p<0.05). And splitting into three different TSH level groups (1st group; <79 microIU/mL, 2nd group; 79-121 microIU/mL, 3rd group; >121 microIU/mL), all values did not have a statistical significant meaning except Apo A1. CONCLUSION: Short-term hypothyroidism induced worsening of lipid metabolic parameters, but not enough to induce the cardiovascular risk in patients with thyroid cancer.
Alanine Transaminase ; Apolipoprotein A-I ; Apolipoproteins ; Apolipoproteins B ; Aspartate Aminotransferases ; Bilirubin ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Cystatin C ; Diabetes Mellitus ; Homocysteine ; Humans ; Hypertension ; Hypothyroidism ; Iodine* ; Lipoprotein(a) ; Reference Values ; Thyroid Neoplasms ; Thyrotropin ; Thyroxine ; Triglycerides ; Uric Acid

OBJECTIVETo detect and identify the potential specific serum biomarkers for diagnosis of papillary thyroid cancer.

METHODSSamples of 35 patients with papillary thyroid carcinoma, 40 patients with benign thyroid nodule and 34 healthy individuals were analyzed using the SELDI-TOF ProteinChip System and bioinfomation technology to find the differential peaks which were separated by HPLC and then further analyzed by LC-MS/MS. The protein sequences were analyzed by SEQUEST software and searched in Bioworks database.

RESULTSThe top six mass-to-charge ratio (M/Z) peaks with the smallest P value were 6651, 6452, 7653, 7932, 15 106 and 15 848 Da, respectively. The 6651 and 6452 Da proteins were weakly expressed in papillary thyroid carcinoma but highly expressed in benign thyroid nodules and healthy individuals. The differences had statistical significance (P < 0.01). The 7653, 7932, 15 106, 15 848 Da proteins were highly expressed in papillary thyroid carcinoma but weakly expressed in benign thyroid nodules and healthy individuals. The differences were statistically significant (P < 0.01). Combination of these six proteins, using the method of leave-one-out to make crossing detection, the specificity of discriminating papillary thyroid carcinoma and non-cancer was 88.0%, and its sensitivity was 92.5%. The 6651 and 6452 Da proteins were identified as apolipoprotein C-I and apolipoprotein C-III, respectively. The 7653 and 15 106 Da proteins were identified as the same protein-alpha-globin, and the 7932 and 15,848 Da proteins were identified as the same protein-beta-globin.

CONCLUSIONThe detection of differentially expressed apolipoprotein C-I, apolipoprotein C-III, alpha-globin, and beta-globin may have utility for diagnosis of papillary thyroid carcinoma and are worthy of further investigation.

Adult ; Apolipoprotein C-I ; blood ; Apolipoprotein C-III ; blood ; Biomarkers, Tumor ; blood ; Carcinoma, Papillary ; blood ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; Protein Array Analysis ; Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Thyroid Neoplasms ; blood ; diagnosis ; alpha-Globins ; metabolism ; beta-Globins ; metabolism