Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study
Abstract Thrombocytopenia is a condition where the platelet count is under 100 × 109/L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymo...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-10631-z |
| _version_ | 1818060668905979904 |
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| author | Ding-Ping Chen Wei-Tzu Lin Ying-Hao Wen Wei-Ting Wang |
| author_facet | Ding-Ping Chen Wei-Tzu Lin Ying-Hao Wen Wei-Ting Wang |
| author_sort | Ding-Ping Chen |
| collection | DOAJ |
| description | Abstract Thrombocytopenia is a condition where the platelet count is under 100 × 109/L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymorphisms (SNPs) of genes related to T cell activation. There were 32 ITP patients and 30 healthy controls enrolled in this study. PCR and sequencing were used to find out the significant SNPs, which we focused on the promoter region of CTLA4 and CD28. In this study, the ITP cases were divided into primary ITP group, secondary ITP group, and the combination of the two to the follow-up analysis. Moreover, dual-luciferase reporter assay was used to evaluate the transcription activity of the significant SNP. We found the − 1765_rs11571315 of CTLA4 gene was associated with primary ITP (p = 0.006), secondary ITP (p = 0.008), and the combination of the two (p = 0.003). Moreover, the −318_rs5742909 also had statistical significance in secondary ITP group that was only caused by autoimmune disease (p = 0.019). In functional study, the rs5742909 would decrease 19% of the transcription activity when it carried a T-allele at this position (p = 0.040). It was noted that CTLA4 gene polymorphism was related to ITP but not CD28. According to our results, we surmised that CTLA4 is involved in the pathogenesis of ITP, and the secondary ITP result from the lower CTLA4 expression that leads to T cell over-activation. |
| first_indexed | 2024-12-10T13:36:05Z |
| format | Article |
| id | doaj.art-92ad6b8f0e904b0e9de41c2f8e2f1965 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-10T13:36:05Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-92ad6b8f0e904b0e9de41c2f8e2f19652022-12-22T01:46:50ZengNature PortfolioScientific Reports2045-23222022-04-011211810.1038/s41598-022-10631-zInvestigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional studyDing-Ping Chen0Wei-Tzu Lin1Ying-Hao Wen2Wei-Ting Wang3Department of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalDepartment of Laboratory Medicine, Linkou Chang Gung Memorial HospitalAbstract Thrombocytopenia is a condition where the platelet count is under 100 × 109/L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymorphisms (SNPs) of genes related to T cell activation. There were 32 ITP patients and 30 healthy controls enrolled in this study. PCR and sequencing were used to find out the significant SNPs, which we focused on the promoter region of CTLA4 and CD28. In this study, the ITP cases were divided into primary ITP group, secondary ITP group, and the combination of the two to the follow-up analysis. Moreover, dual-luciferase reporter assay was used to evaluate the transcription activity of the significant SNP. We found the − 1765_rs11571315 of CTLA4 gene was associated with primary ITP (p = 0.006), secondary ITP (p = 0.008), and the combination of the two (p = 0.003). Moreover, the −318_rs5742909 also had statistical significance in secondary ITP group that was only caused by autoimmune disease (p = 0.019). In functional study, the rs5742909 would decrease 19% of the transcription activity when it carried a T-allele at this position (p = 0.040). It was noted that CTLA4 gene polymorphism was related to ITP but not CD28. According to our results, we surmised that CTLA4 is involved in the pathogenesis of ITP, and the secondary ITP result from the lower CTLA4 expression that leads to T cell over-activation.https://doi.org/10.1038/s41598-022-10631-z |
| spellingShingle | Ding-Ping Chen Wei-Tzu Lin Ying-Hao Wen Wei-Ting Wang Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study Scientific Reports |
| title | Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study |
| title_full | Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study |
| title_fullStr | Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study |
| title_full_unstemmed | Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study |
| title_short | Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study |
| title_sort | investigation of the correlation between immune thrombocytopenia and t cell activity regulated gene polymorphism using functional study |
| url | https://doi.org/10.1038/s41598-022-10631-z |
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