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.
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 (...
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Public Library of Science (PLoS)
2018-06-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0006547&type=printable |
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| author | Bo Xing Xiao-Kun Li Shao-Fei Zhang Qing-Bin Lu Juan Du Pan-He Zhang Zhen-Dong Yang Ning Cui Chen-Tao Guo Wu-Chun Cao Xiao-Ai Zhang Wei Liu Wei Liu |
| author_facet | Bo Xing Xiao-Kun Li Shao-Fei Zhang Qing-Bin Lu Juan Du Pan-He Zhang Zhen-Dong Yang Ning Cui Chen-Tao Guo Wu-Chun Cao Xiao-Ai Zhang Wei Liu Wei Liu |
| author_sort | Bo Xing |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c4bf11617ea943678eed73a2bd5e7d7b |
| institution | DOAJ |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2018-06-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-c4bf11617ea943678eed73a2bd5e7d7b2025-08-20T02:46:00ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352018-06-01126e000654710.1371/journal.pntd.0006547Polymorphisms 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.Bo XingXiao-Kun LiShao-Fei ZhangQing-Bin LuJuan DuPan-He ZhangZhen-Dong YangNing CuiChen-Tao GuoWu-Chun CaoXiao-Ai ZhangWei LiuWei LiuSevere 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.https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0006547&type=printable |
| spellingShingle | Bo Xing Xiao-Kun Li Shao-Fei Zhang Qing-Bin Lu Juan Du Pan-He Zhang Zhen-Dong Yang Ning Cui Chen-Tao Guo Wu-Chun Cao Xiao-Ai Zhang Wei Liu Wei Liu 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. PLoS Neglected Tropical Diseases |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0006547&type=printable |
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