Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-n...
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00744/full |
| _version_ | 1811316228187226112 |
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| author | Ju Li Sai Ma Linlin Shao Chunhong Ma Chengjiang Gao Xiao-hui Zhang Ming Hou Ming Hou Jun Peng |
| author_facet | Ju Li Sai Ma Linlin Shao Chunhong Ma Chengjiang Gao Xiao-hui Zhang Ming Hou Ming Hou Jun Peng |
| author_sort | Ju Li |
| collection | DOAJ |
| description | Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP. We recruited 312 ITP inpatients and 154 healthy participants in this case–control study. Inflammation-related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR. All SNPs in healthy controls were consistent with Hardy–Weinberg equilibrium. Statistical analysis revealed that rs10499194 in TNFAIP3 was significantly associated with a decreased risk of ITP after Bonferroni multiple correction (codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262–0.711, p = 0.001; dominant, TT/CT vs. CC, OR = 0.249, 95% CI = 0.141–0.440, p = 0.000). Besides, TNFAIP3 expression was significantly higher in patients with CT and pooled CT/TT genotypes compared with CC genotype (p = 0.001; p = 0.001). Interestingly, rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT vs. CC, OR = 0.092, 95% CI = 0.021–0.398, p = 0.001; dominant, TT/CT vs. CC, OR = 0.086, 95% CI = 0.020–0.369, p = 0.001; allelic, T vs. C, OR = 0.088, 95% CI = 0.021–0.372, p = 0.001). Furthermore, no significant association was found between inflammation-related SNPs and the severity or refractoriness of ITP after Bonferroni multiple correction. Our findings suggest that rs10499194 may be a protective factor for susceptibility and corticosteroid sensitivity in ITP patients. |
| first_indexed | 2024-04-13T11:46:15Z |
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| id | doaj.art-9afd0034b8044ddeb2eda7f3c8c946df |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T11:46:15Z |
| publishDate | 2017-06-01 |
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| spelling | doaj.art-9afd0034b8044ddeb2eda7f3c8c946df2022-12-22T02:48:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00744265036Inflammation-Related Gene Polymorphisms Associated With Primary Immune ThrombocytopeniaJu Li0Sai Ma1Linlin Shao2Chunhong Ma3Chengjiang Gao4Xiao-hui Zhang5Ming Hou6Ming Hou7Jun Peng8Department of Hematology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Immunology, Shandong University School of Medicine, Jinan, ChinaDepartment of Immunology, Shandong University School of Medicine, Jinan, ChinaBeijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University People’s Hospital, Beijing, ChinaDepartment of Hematology, Qilu Hospital, Shandong University, Jinan, ChinaShandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Hematology, Qilu Hospital, Shandong University, Jinan, ChinaPrimary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by a reduced platelet count and an increased risk of bleeding. Although immense research has improved our understanding of ITP, the pathogenesis remains unclear. Here, we investigated the involvement of 25 single-nucleotide polymorphisms (SNPs) of the inflammation-related genes, including CD24, CD226, FCRL3, IL2, IRF5, ITGAM, NLRP3, CARD8, PTPN22, SH2B2, STAT4, TNFAIP3, and TRAF1, in the pathogenesis and treatment response of ITP. We recruited 312 ITP inpatients and 154 healthy participants in this case–control study. Inflammation-related SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. The expression of TNFAIP3 mRNA was determined by quantitative real-time RT-PCR. All SNPs in healthy controls were consistent with Hardy–Weinberg equilibrium. Statistical analysis revealed that rs10499194 in TNFAIP3 was significantly associated with a decreased risk of ITP after Bonferroni multiple correction (codominant, CT vs. CC, OR = 0.431, 95% CI = 0.262–0.711, p = 0.001; dominant, TT/CT vs. CC, OR = 0.249, 95% CI = 0.141–0.440, p = 0.000). Besides, TNFAIP3 expression was significantly higher in patients with CT and pooled CT/TT genotypes compared with CC genotype (p = 0.001; p = 0.001). Interestingly, rs10499194 was also associated with corticosteroid-sensitivity (codominant, CT vs. CC, OR = 0.092, 95% CI = 0.021–0.398, p = 0.001; dominant, TT/CT vs. CC, OR = 0.086, 95% CI = 0.020–0.369, p = 0.001; allelic, T vs. C, OR = 0.088, 95% CI = 0.021–0.372, p = 0.001). Furthermore, no significant association was found between inflammation-related SNPs and the severity or refractoriness of ITP after Bonferroni multiple correction. Our findings suggest that rs10499194 may be a protective factor for susceptibility and corticosteroid sensitivity in ITP patients.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00744/fullprimary immune thrombocytopeniainflammationsingle-nucleotide polymorphismsusceptibilitytreatment |
| spellingShingle | Ju Li Sai Ma Linlin Shao Chunhong Ma Chengjiang Gao Xiao-hui Zhang Ming Hou Ming Hou Jun Peng Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia Frontiers in Immunology primary immune thrombocytopenia inflammation single-nucleotide polymorphism susceptibility treatment |
| title | Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia |
| title_full | Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia |
| title_fullStr | Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia |
| title_full_unstemmed | Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia |
| title_short | Inflammation-Related Gene Polymorphisms Associated With Primary Immune Thrombocytopenia |
| title_sort | inflammation related gene polymorphisms associated with primary immune thrombocytopenia |
| topic | primary immune thrombocytopenia inflammation single-nucleotide polymorphism susceptibility treatment |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00744/full |
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