7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Polymorphisms and haplotypes in the promoter of the TNF-α gene are associated with disease severity of severe fever with thrombocytopenia syndrome in Chinese Han population

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha ( TNF-α) were associated with risk to severity of SFTS. Five TNF-α SNPs (SNP1: T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected subjects of Chinese Han origin. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A A allele than those with mild/asymptomatic infection ( P = 0.006). Furthermore, T-1031C C allele ( P < 0.001) and G-238A A allele ( P < 0.001) were significantly associated with decreased risk of death. Multiple haplotypes were significantly associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3, CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4, ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA assay, we observed that TNF-α concentration of hospitalized patients was significantly increased in acute phase than in convalescent phase ( P < 0.001). Elevated TNF-α concentration was also revealed from fatal patients ( P < 0.001). The -238A allele was associated with decreased serum TNF-α levels in SFTS patients in acute phase ( P = 0.01). Our findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population.

          Author summary

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus. The current study disclosed the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha ( TNF-α) were associated with risk to disease severity of SFTS. These findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population. The study will be of interest to either the clinicians devoted to the prevention and therapy of SFTS or the geneticists devoted to studying the genetic susceptibility mechanisms of common diseases.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome.

          Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in China, caused by SFTS virus (SFTSV). Severe SFTS patients can quickly proceed to multiorgan dysfunction and death; however, underlying pathogenic mechanisms remain unclear. Serum samples from 15 fatal and 44 nonfatal SFTS cases were subjected to multiplex-microbead immunoassays to detect a broad spectrum of cytokines. The viral load and virus-specific IgG titers were also tested by real-time PCR and ELISA, respectively. Cytokines IL-1RA, IL-6, IL-10, G-CSF, IP-10, and MCP-1 were elevated in SFTS patients and produced at robust levels in fatal cases. In contrast, cytokines PDGF-BB and RANTES decreased in SFTS patients. These cytokines reverted to normal ranges during the convalescent phase of SFTSV infection. Cytokines IL-1β, IL-8, MIP-1α, and MIP-1β showed a unique pattern of elevation in fatal cases but not in nonfatal cases. However, these cytokines increased in the convalescent phase of nonfatal SFTS cases. Our regression analysis revealed that the serum viral load correlated with these cytokines. Moreover, levels of these cytokines correlated with various clinical parameters and virus-specific IgG titers. The study demonstrates that SFTSV infection induces a cytokine storm with abnormally expressed cytokine profiles, which are associated with the disease severity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Current status of severe fever with thrombocytopenia syndrome in China.

            Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV). SFTSV is associated with a high mortality rate and has been reported in China, South Korea and Japan. SFTSV undergoes rapid changes owing to evolution, gene mutations, and reassortment between different strains of SFTSV. In this review, we summarize the recent cases and general properties of SFTS, focusing on the epidemiology, genetic diversity, clinical features, and diagnostics of SFTSV in China. From 2010 to October 2016, SFTS cases were reported in 23 provinces of China, with increased numbers yearly. Infection and death cases are mainly found in central China, where the Haemaphysalis longicornis ticks are spread. The national average mortality rate of SFTS infection was 5.3%, with higher risk to elder people. The main epidemic period was from May to July, with a peak in May. Thus, SFTS reminds a significant public health problem, and development of prophylactic vaccines and effective antiviral drugs will be highly needed.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome.

              The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)-infected patients. A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011-2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023-1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660-10.948; P 1200 U/L; OR, 2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.
                Bookmark

                Author and article information

                Contributors
                Role: Data curationRole: InvestigationRole: Methodology
                Role: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: MethodologyRole: Resources
                Role: Data curationRole: MethodologyRole: Resources
                Role: Formal analysisRole: InvestigationRole: Methodology
                Role: Data curationRole: MethodologyRole: Project administration
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Software
                Role: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                25 June 2018
                June 2018
                : 12
                : 6
                : e0006547
                Affiliations
                [1 ] State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, P. R, China
                [2 ] School of Public Health, Peking University, Beijing, P. R, China
                [3 ] The 154 Hospital, People’s Liberation Army, Xinyang, P. R, China
                CDC, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-9302-8170
                Article
                PNTD-D-18-00286
                10.1371/journal.pntd.0006547
                6034906
                29939989
                9a753ea9-a5a2-44ea-8087-2494276d6d92
                © 2018 Xing et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 February 2018
                : 20 May 2018
                Page count
                Figures: 2, Tables: 4, Pages: 14
                Funding
                Funded by: Foundation for Innovative Research Groups of the National Natural Science Foundation of China
                Award ID: 81621005
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 81473023
                Award Recipient :
                Funded by: National Natural Science Foundation of China
                Award ID: 81673231
                Award Recipient :
                Funded by: the China Mega-Project on Infectious Disease Prevention
                Award ID: 2018ZX10713002
                Award Recipient :
                Funded by: the China Mega-Project on Infectious Disease Prevention
                Award ID: 2018ZX10301401-005
                Award Recipient :
                This work was supported by Foundation for the China Mega-Project on Infectious Disease Prevention (No. 2018ZX10713002, 2018ZX10301401-005), National Natural Science Foundation of China (No. 81473023, 81673231) and Innovative Research Groups of the National Natural Science Foundation of China (No. 81621005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Molecular Genetics
                Biology and Life Sciences
                Molecular Biology
                Molecular Genetics
                Biology and Life Sciences
                Genetics
                Heredity
                Genetic Mapping
                Haplotypes
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Cytokines
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Cytokines
                Biology and Life Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Medicine and Health Sciences
                Immunology
                Immune System
                Innate Immune System
                Cytokines
                Biology and Life Sciences
                Developmental Biology
                Molecular Development
                Cytokines
                Biology and Life Sciences
                Genetics
                Heredity
                Genetic Mapping
                Variant Genotypes
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Fevers
                Medicine and Health Sciences
                Hematology
                Thrombocytopenia
                People and places
                Population groupings
                Ethnicities
                Chinese people
                Han Chinese people
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Custom metadata
                vor-update-to-uncorrected-proof
                2018-07-06
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article