SIRT1 single-nucleotide polymorphisms are associated with corticosteroid sensitivity in primary immune thrombocytopenia patients

Wang, Shuwen; Zhang, Xiaoyu; Leng, Shaoqiu; Zhang, Yanqi; Ju, Li; Peng, Jun; Zhou, Zeping; Feng, Qi; Hu, Xiang

doi:10.1007/s00277-021-04583-z

Cited by 3 publications

(7 citation statements)

References 47 publications

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“…Recently, many studies have identified genes associated with the risk of glucocorticoid treatment failure and development of CITP include SIRT1 (rs12778366 and rs4746720),15 SDF1 (rs266085),10,16 ABCB1 (C1235T, G2677T/A, and C3435T),17 TNFα (-308AG)18 and IL-23R (rs1884444) 19. In our previous study, we demonstrated that the percentage of Th17/Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage.…”

Section: Discussionmentioning

confidence: 86%

“…So, the specific SNP may not be associated with the development of CITP in this cohort. In addition, SNPs ( STAT1 ,1 TNFβ ,9 IL-17F ,12,13 SDF1 ,10 and FCGRIIb 14) associated with development of CITP are different from SNPs ( SIRT1 ,15 SDF1 ,10,16 ABCB1 ,17 TNFα ,18 and IL-23R 19) associated corticosteroid sensitivity except SDF1 . Therefore, studies on ITP chronicity and treatment-sensitivity should be carried out separately.…”

Section: Discussionmentioning

confidence: 90%

“…These SNPs might represent a useful predictive biomarker of the disease course. The SIRT1 ,15 SDF1 ,10,16 ABCB1 ,17 TNFα ,18 and IL-23R 19 genes have been associated with therapy resistance especially corticosteroid sensitivity.…”

mentioning

confidence: 99%

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Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

Gu¹,

Xie

Ma³

et al. 2022

Journal of Pediatric Hematology/Oncology

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Background: Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases, suggesting that HIF1α may be involved in immune dysregulation in patients with immune thrombocytopenia (ITP). The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) of the HIF1A gene are associated with susceptibility to ITP and its clinical prognosis including incidence of chronic ITP and glucocorticoid sensitivity. Materials and Methods:This study involved 197 Chinese ITP pediatric patients (discovery cohort) and 220 healthy controls. The Sequenom MassArray system (Sequenom, San Diego, CA) was used to detect 3 SNPs genotypes in the HIF1A gene: rs11549465, rs1957757, and rs2057482. We also used another ITP cohort (N = 127) to validate the significant results of SNPs found in the discovery cohort.Results: The frequencies of the three SNPs did not show any significant differences between the ITP and healthy control groups. The CT genotype at rs11549465 was significantly higher in ITP patients sensitive to glucocorticoid treatment than in those insensitive to glucocorticoid treatment (P = 0.025). These results were validated using another ITP cohort (N = 127, P = 0.033). Moreover, the CC genotype was a risk factor for insensitive to GT the odds ratio (95% confidence interval) was 5.96 (5.23-6.69) in standard prednisone (P = 0.0069) and 6. 35 (5.33-7.37) in high-dose dexamethasone (P = 0.04).Conclusions: Although HIF1A gene polymorphisms were not associated with susceptibility to ITP, the CT genotype at rs11549465 was associated with the sensitivity to glucocorticoid treatment of ITP patients, suggesting that the rs11549465 SNP may contribute to the sensitivity of glucocorticoid treatment in pediatric ITP patients.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 90%

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Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

Gu¹,

Xie

Ma³

et al. 2022

Journal of Pediatric Hematology/Oncology

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“…49 In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a half-fold decreased risk of corticosteroid resistance. 49 They suggested that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.…”

Section: Ge N Etic M a R K Er Smentioning

confidence: 99%

“…48 Wang et al 49 investigated the contribution of the SIRT1 SNPs rs12778366 and rs4746720 in 330 patients and found that the CC/TC genotypes of SIRT1 rs12778366 were associated with a twofold increased risk of corticosteroid resistance compared to the homozygous major TT genotype. 49 In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a half-fold decreased risk of corticosteroid resistance. 49 They suggested that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.…”

Section: Ge N Etic M a R K Er Smentioning

confidence: 99%

The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

Yazdanbakhsh,

Provan,

Semple

2023

Br J Haematol

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SummaryImmune thrombocytopenia (ITP) is characterized by a dysregulated immune response against platelets, affecting both their destruction and production. A role for an abnormal T‐cell compartment has been established in ITP pathogenesis and treatments that increase platelet counts in patients with ITP have shown improvements in T‐cell profiles. On the other hand, patients who were refractory to treatment appear to retain the T‐cell abnormalities as before. Myeloid‐derived suppressive cells (MDSCs) are also emerging as key contributors to the immune pathology of ITP and response to treatment. In this review, we will discuss how various treatments affect the T‐cell and MDSC compartments in ITP. The review will focus on studies that have examined the underlying mechanisms and/or genetic basis responsible for refractoriness to a given treatment and highlight remaining challenges in identifying factors and mechanisms to predict response to treatment.

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Predicting the efficacy of glucocorticoids in pediatric primary immune thrombocytopenia using plasma proteomics

Cao,

Zhu,

et al. 2023

Front. Immunol.

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ObjectivePrimary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics.MethodsA four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method.Results47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers.ConclusionThis study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.

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SIRT1 single-nucleotide polymorphisms are associated with corticosteroid sensitivity in primary immune thrombocytopenia patients

Cited by 3 publications

References 47 publications

Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

Predicting the efficacy of glucocorticoids in pediatric primary immune thrombocytopenia using plasma proteomics

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