1
|
Ye S, Chen Y, Lou X, Ye X, Yang X. Association of macrophage inhibitory factor -1 polymorphisms with antiviral efficacy of type 1b chronic hepatitis C. Mol Cell Biochem 2021; 476:2439-2447. [PMID: 33604810 PMCID: PMC8119258 DOI: 10.1007/s11010-021-04097-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 02/04/2021] [Indexed: 11/09/2022]
Abstract
The expression of macrophage inhibitory factor-1 (MIC-1) increases in patients with chronic hepatitis C (CHC), but whether MIC-1 level and its polymorphism affect the antiviral efficacy of CHC has not yet been reported. The present study aimed to investigate the association between MIC-1 polymorphism and antiviral efficacy in patients with CHC genotype 1b (CHC 1b). A total of 171 patients with CHC1b were recruited. The polymorphisms of rs1059369 and rs1059519 in MIC-1 were detected by DNA sequencing. All patients received a standard dose of polyethylene glycol interferon + ribavirin (PR regimen), and divided into response, nonresponse, sustained virological response (SVR), and non-sustained virological response (NSVR) groups based on HCV RNA levels. The genotype distribution of the two single nucleotide polymorphisms (SNPs) did not differ between the response and nonresponse groups, SVR and non-SVR groups. However, the level of MIC-1 was positively correlated with ALT, AST, PIIINP, CIV, and HCV RNA (P < 0.05). Compared to before treatment, the level of MIC-1 in plasma was significantly decrease in the response group but not in the non-responsive group. Our results suggest that the level of MIC-1 in CHC1b is correlated with liver cell injury, liver fibrosis index, and viral load. However, the polymorphism of rs1059369 and rs1059519 may have negligible impact in expression of MIC-1 and efficacy of antiviral therapy in CHC patient.
Collapse
Affiliation(s)
- Songdao Ye
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yao Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaoting Lou
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xuanmei Ye
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xunjun Yang
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
- Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.
| |
Collapse
|
2
|
Yang XJ, Wang XO, Chen Y, Ye SD. Associations of content and gene polymorphism of macrophage inhibitory factor-1 and chronic hepatitis C virus infection. World J Gastroenterol 2020; 26:6378-6390. [PMID: 33244199 PMCID: PMC7656212 DOI: 10.3748/wjg.v26.i41.6378] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/07/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The expression of macrophage inhibitory factor-1 (MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.
AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus (HCV) infection.
METHODS This case-control study enrolled 178 patients with chronic hepatitis C (CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.
RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group (P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase (AST), type III procollagen N-terminal peptide (known as PIIINP), type IV collagen, and HCV RNA (P < 0.05), whereas negatively correlated with total protein and albumin (P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups (P < 0.05). The allele frequency maintained significant difference after Bonferroni correction (Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC (P < 0.05). Linkage disequilibrium (LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups (P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes (P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype (P = 0.009, after Bonferroni correction).
CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.
Collapse
Affiliation(s)
- Xun-Jun Yang
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
| | - Xiao-Ou Wang
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
| | - Yao Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325006, Zhejiang Province, China
| | - Song-Dao Ye
- Department of Laboratory Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
| |
Collapse
|
3
|
Plasma Growth Differentiation Factor-15 is a Potential Biomarker for Pediatric Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. Pediatr Cardiol 2017; 38:1620-1626. [PMID: 28819713 DOI: 10.1007/s00246-017-1705-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2016] [Accepted: 08/07/2017] [Indexed: 12/18/2022]
Abstract
We aimed to investigate plasma growth differentiation factor-15 (GDF-15) levels in pediatric pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), and assess the association with hemodynamic parameters. Plasma GDF-15 levels were measured in children with PAH-CHD (n = 46) and compared to children with CHD without PAH (n = 39). Normal individuals (n = 30) served as health control group. Plasma GDF-15 levels were significantly elevated in patients with PAH-CHD compared with those with CHD without PAH (median 1415 ng/L, interquartile range [IQR] 926.7-2111.7 ng/L vs. 890.6 ng/L, IQR 394.7-1094.3 ng/L, p < 0.01). Elevated plasma GDF-15 levels were positively related to Functional Class, uric acid, N-terminal pro-B-type natriuretic peptide (NT-proBNP), pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary blood flow/systemic blood flow and pulmonary vascular resistance, and a lower mixed venous oxygen saturation (Svo2). The area under the curve (AUC) for adding GDF-15 to NT-proBNP was not superior to the AUC of NT-pro BNP alone (AUC difference 0.0295, p = 0.324) (NT-proBNP, AUC 0.823, 95% CI 0.725-0.897; GDF-15 plus NT-proBNP, AUC 0.852, 95% CI 0.759-0.92), whereas it revealed a slightly greater specificity and positive predictive value. The diagnostic power of NT-pro BNP was not inferior to GDF-15 (AUC difference 0.0443, p = 0.43). Plasma GDF-15 levels might be a surrogate marker for pediatric PAH-CHD.
Collapse
|
4
|
Xiang Y, Zhang T, Guo J, Peng YF, Wei YS. The Association of Growth Differentiation Factor-15 Gene Polymorphisms with Growth Differentiation Factor-15 Serum Levels and Risk of Ischemic Stroke. J Stroke Cerebrovasc Dis 2017; 26:2111-2119. [PMID: 28526273 DOI: 10.1016/j.jstrokecerebrovasdis.2017.04.031] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Revised: 04/22/2017] [Accepted: 04/26/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Current evidence shows that growth differentiation factor-15 (GDF-15) plays an important role in the progression of ischemic stroke (IS). The aim of this study was to investigate the association between 3 single-nucleotide polymorphisms of the GDF-15 gene and IS susceptibility in the Chinese population. MATERIALS AND METHODS The study subjects comprised 601 Chinese individuals, including 298 stroke patients and 303 age- and gender-matched healthy controls. The polymorphisms were measured using snapshot single-nucleotide polymorphism genotyping assays and confirmed by sequencing. Serum GDF-15 (sGDF-15) levels were measured by enzyme-linked immunosorbent assay. RESULTS The distribution of rs1804826G/T polymorphism was significant different between the 2 groups (P < .05). Compared with the rs1804826 G allele, the rs1804826 T allele was significantly associated with an increased risk of IS (P < .05). Haplotype analyses showed that the T-T-G haplotype was significantly associated with an increased risk of IS (odds ratio = 1.671, 95% confidence interval = 1.231-2.268; P = .001). Compared with the normal controls, the sGDF-15 levels were significantly increased in stroke patients (P < .001). Besides, patients carrying rs1804826 GT/TT genotypes had higher sGDF-15 levels compared with those carrying GG genotypes (P < .05). CONCLUSIONS The GDF-15 gene rs1804826G/T polymorphism and sGDF-15 levels are associated with IS in the Chinese population. Our data indicate that the GDF-15 gene may play a role in the development of IS.
Collapse
Affiliation(s)
- Yang Xiang
- Department of Clinical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Ting Zhang
- Department of Clinical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Jing Guo
- Department of Dermatology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - You-Fan Peng
- Department of Clinical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Ye-Sheng Wei
- Department of Clinical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
| |
Collapse
|
5
|
Recent Advances in Biomarker Discovery — from Serum to Imaging-based Biomarkers for a Complex Assessment of Heart Failure Patients. JOURNAL OF INTERDISCIPLINARY MEDICINE 2016. [DOI: 10.1515/jim-2016-0045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Abstract
Over the last years, a vast majority of serum biomarkers and imaging techniques have been used alone or combined in the diagnosis, management and prognosis of numerous pathologies. This review provides a brief insight into the novelties from the last 6 years (2010–2016) regarding serum and imaging markers in heart failure (HF). New information about natriuretic peptides (NPs), soluble ST2 (Sst2), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), C-reactive protein (CRP), procalcitonin (PCT), troponins (Tns), myoglobin (Mb), galectin-3 (Gal-3), micro ribonucleic acids (microRNAs) and long non-coding ribonucleic acids (IncRNAs), copectin and cardiac magnetic resonance (CMR) measurements were summarized in this review in order to guide the practitioner.
Collapse
|
6
|
Berezin AE. Prognostication in Different Heart Failure Phenotypes: The Role of Circulating Biomarkers. J Circ Biomark 2016; 5:6. [PMID: 28936254 PMCID: PMC5548324 DOI: 10.5772/62797] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Accepted: 03/02/2016] [Indexed: 12/11/2022] Open
Abstract
Heart failure (HF) is multifactorial syndrome with high cardiovascular (CV) morbidity and mortality rates associated with an increasing prevalence worldwide. Measuring plasma levels of circulating biomarkers, i.e., natriuretic peptides, cardiac-specific troponins, metabolomic intermediates, Galectin-3, ST2, cardiotrophin-1, soluble endoglin and growth differentiation factor 15, may assist in the prognostication of HF development. However, the role of biomarker models in the prediction of an early stage of HF with a preserved ejection fraction (HFpEF) and HF with a reduced ejection fraction (HFrEF) is not still understood. This review explores the knowledge regarding the utility of cardiac biomarkers, aiming to reclassify patients with different phenotypes of HF. The review reports that several biomarkers reflected on subsequently alter collagen turnover, cardiac fibrosis and inflammation, which might have diagnostic and predictive value in HFpEF and HFrEF. The best candidates for determining the early stage of HF development were sST2, Galectin-3, CT-1 and GDF-15. However, increased plasma concentrations of these biomarkers were not specific to a distinct disease group of HFpEF and HFrEF. Finally, more investigations are required to determine the role of novel biomarkers in the prediction of HF and the determination of the early stages of HFpEF and HFrEF development.
Collapse
|
7
|
Berezin AE. Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15. Diabetes Metab Syndr 2016; 10:S154-S157. [PMID: 26482961 DOI: 10.1016/j.dsx.2015.09.016] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 09/27/2015] [Indexed: 12/23/2022]
Abstract
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which belongs to super family of the transforming growth factor beta. GDF-15 is widely presented in the various cells (macrophages, vascular smooth muscle cells, adipocytes, cardiomyocytes, endothelial cells, fibroblasts), tissues (adipose tissue, vessels, tissues of central and peripheral nervous system) and organs (heart, brain, liver, placenta) and it plays an important role in the regulation of the inflammatory response, growth and cell differentiation. Elevated GDF-15 was found in patients with established CV diseases including hypertension, stable coronary artery disease, acute coronary syndrome, myocardial infarction, ischemic and none ischemic-induced cardiomyopathies, heart failure, atrial fibrillation, as well as stroke, type two diabetes mellitus (T2DM), chronic kidney disease, infection, liver cirrhosis, malignancy. Therefore, aging, smoking, and various environmental factors, i.e. chemical pollutants are other risk factors that might increase serum GDF-15 level. Although GDF-15 has been reported to be involved in energy homoeostasis and weight loss, to have anti-inflammatory properties, and to predict CV diseases and CV events in general or established CV disease population, there is no large of body of evidence regarding predictive role of elevated GDF-15 in T2DM subjects. The mini review is clarified the role of GDF-15 in T2DM subjects.
Collapse
Affiliation(s)
- Alexander E Berezin
- Internal Medicine Department, State Medical University, 26, Mayakovsky av., Zaporozhye 69035, Ukraine.
| |
Collapse
|
8
|
Tantawy AAG, Adly AAM, Ismail EAR, Youssef OI, Ali ME. Growth differentiation factor-15 in children and adolescents with thalassemia intermedia: Relation to subclinical atherosclerosis and pulmonary vasculopathy. Blood Cells Mol Dis 2015; 55:144-50. [PMID: 26142330 DOI: 10.1016/j.bcmd.2015.06.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 06/02/2015] [Accepted: 06/05/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND Heart disease is the leading cause of mortality and one of the main causes of morbidity in β-thalassemia. Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily, is a marker of ineffective erythropoiesis in several anemias. AIM To determine GDF-15 levels in children and adolescents with TI and the relation to hemolysis, iron overload and cardiovascular complications. METHODS GDF-15 was measured in 35 TI patients without symptoms for heart disease and correlated to echocardiographic parameters and carotid intima media thickness (CIMT). RESULTS GDF-15 levels were significantly higher in TI patients compared with controls (p < 0.001). Transfusion dependent patients had higher GDF-15 than non-transfusion dependent patients. TI patients with splenectomy, pulmonary hypertension risk, and heart disease had higher GDF-15 levels than those without. GDF-15 was lower among hydroxyurea-treated patients. Multiple linear regression analysis revealed that transfusion index (p=0.012), serum ferritin (p < 0.001), tricuspid regurgitant jet velocity (p < 0.001), ejection fraction (p=0.01) and CIMT (p=0.007) were independently related to GDF-15. According to ROC curve analysis, the cutoff value of GDF-15 at 1500 pg/mL could differentiate patients with and without heart disease. CONCLUSION GDF-15 would identify TI patients at increased risk of pulmonary and cardiovascular complications as well as subclinical atherosclerosis.
Collapse
Affiliation(s)
| | | | | | | | - Mohamed ElSayed Ali
- Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| |
Collapse
|