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

Autor: Wu-Chun Cao, Zhen-Dong Yang, Juan Du, Wei Liu, Qing-Bin Lu, Bo Xing, Ning Cui, Shao-Fei Zhang, Pan-He Zhang, Xiao-Ai Zhang, Chen-Tao Guo, Xiao-Kun Li
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Heredity
Physiology
Fevers
Artificial Gene Amplification and Extension
Pathology and Laboratory Medicine
Han Chinese people
Polymerase Chain Reaction
Gastroenterology
Polymorphism (computer science)
Immune Physiology
Medicine and Health Sciences
Ethnicities
Promoter Regions
Genetic
Innate Immune System
lcsh:Public aspects of medicine
Hematology
Middle Aged
Population groupings
Genetic Mapping
Infectious Diseases
Cytokines
Female
Tumor necrosis factor alpha
medicine.symptom
Research Article
Risk
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Immunology
Variant Genotypes
Single-nucleotide polymorphism
Bunyaviridae Infections
Research and Analysis Methods
Polymorphism
Single Nucleotide
Asymptomatic
Molecular Genetics
03 medical and health sciences
Signs and Symptoms
Asian People
Diagnostic Medicine
Internal medicine
Genetics
medicine
Humans
Allele
Molecular Biology Techniques
Molecular Biology
Alleles
Genetic Association Studies
Aged
Tumor Necrosis Factor-alpha
business.industry
Haplotype
Public Health
Environmental and Occupational Health
Biology and Life Sciences
lcsh:RA1-1270
Odds ratio
Molecular Development
medicine.disease
Thrombocytopenia
Severe fever with thrombocytopenia syndrome
030104 developmental biology
Haplotypes
Immune System
Chinese people
People and places
business
Developmental Biology
Zdroj: PLoS Neglected Tropical Diseases, Vol 12, Iss 6, p e0006547 (2018)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje