HIF1A 基因单核苷酸多态性与儿童特发性血小板减少性紫癜患者糖皮质激素治疗敏感性相关。
Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients.
机构信息
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education.
Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
出版信息
J Pediatr Hematol Oncol. 2023 May 1;45(4):195-199. doi: 10.1097/MPH.0000000000002483. Epub 2022 May 4.
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.
背景
缺氧诱导因子-1α（HIF-1α）在先天和适应性免疫中都起着至关重要的作用。新出现的证据表明，HIF-1α与自身免疫性疾病的炎症和病理活动有关，这表明 HIF1α可能参与了免疫性血小板减少症（ITP）患者的免疫失调。本研究的目的是评估 HIF1A 基因的单核苷酸多态性（SNP）是否与 ITP 的易感性及其临床预后相关，包括慢性 ITP 的发生率和糖皮质激素的敏感性。
材料和方法
本研究纳入了 197 例中国 ITP 儿科患者（发现队列）和 220 例健康对照。使用 Sequenom MassArray 系统（Sequenom，圣地亚哥，CA）检测 HIF1A 基因中的 3 个 SNP 基因型：rs11549465、rs1957757 和 rs2057482。我们还使用另一个 ITP 队列（N=127）来验证在发现队列中发现的 SNP 的显著结果。
结果
ITP 组和健康对照组之间这三个 SNP 的频率没有显示出任何显著差异。在对糖皮质激素治疗敏感的 ITP 患者中，rs11549465 的 CT 基因型明显高于对糖皮质激素治疗不敏感的患者（P=0.025）。这些结果在另一个 ITP 队列（N=127，P=0.033）中得到了验证。此外，CC 基因型是对 GT 不敏感的危险因素，优势比（95%置信区间）在标准泼尼松治疗中为 5.96（5.23-6.69）（P=0.0069），在高剂量地塞米松治疗中为 6.35（5.33-7.37）（P=0.04）。
结论
虽然 HIF1A 基因多态性与 ITP 的易感性无关，但 rs11549465 处的 CT 基因型与 ITP 患者对糖皮质激素治疗的敏感性有关，表明 rs11549465 SNP 可能有助于儿科 ITP 患者对糖皮质激素治疗的敏感性。
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