SIRT1 single-nucleotide polymorphisms are associated with corticosteroid sensitivity in primary immune thrombocytopenia patients
SIRT1 single-nucleotide polymorphisms are associated with corticosteroid sensitivity in primary immune thrombocytopenia patients
复制标题
SIRT1单核苷酸多态性与原发性免疫性血小板减少症患者的皮质类固醇敏感性相关
DOI：
10.1007/s00277-021-04583-z
复制
发表时间：
2021-07-16
影响因子：
3.5
通讯作者：
Hu，Xiang
中科院分区：
文献类型：
--
作者：
Wang，Shuwen;Zhang，Xiaoyu;Hu，Xiang
研究背景原发性免疫性血小板减少症（ITP）是一种以血小板减少为特征的自身免疫性疾病。虽然糖皮质激素是ITP患者有用的一线治疗，但其长期有效性有限，并且ITP患者中糖皮质激素敏感性的决定因素在很大程度上仍然未知。Sirtuin 1（SIRT 1）是哺乳动物Sirtuin家族的成员，与皮质类固醇的抗炎作用有关。在这里，我们调查的贡献SIRT 1单核苷酸多态性（SNPs）rs 12778366和rs 4746720 ITP susceptibility.MethodsWe招募330例ITP患者和309名健康对照从汉族人群，并进行基因分型SIRT 1 rs 12778366和rs 4746720使用MassARRAY系统。结果采用汉族ITP患者和对照组的临床资料，包括糖皮质激素敏感性、敏感性、难治性和严重程度，我们的研究结果显示，与纯合子主要TT基因型相比，SIRT 1 rs 12778366的CC/TC基因型与皮质类固醇抵抗的风险增加2.034倍相关（显性，CC/TC vs. TT，OR = 2.034，95%CI = 1.039- 3.984，p = 0.038）。相比之下，SIRT 1 rs 4746720的CC/CT基因型显示皮质类固醇抵抗的风险降低0.560倍（显性，95%CI = 0.321-0.976，OR = 0.560，p = 0.041）。SIRT 1 rs 12778366中的C等位基因替代与ITP患者的皮质类固醇敏感性显著相关（p= 0.021）。结论SIRT 1基因rs 12778366和rs 4746720可能是影响ITP患者激素敏感性的遗传因素。
BackgroundPrimary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count. While corticosteroids are a useful first-line therapy for ITP patients, their long-term effectiveness is limited, and the determinants of corticosteroid sensitivity in ITP patients remain largely unknown. Sirtuin 1 (SIRT1), a member of the mammalian sirtuin family, is related to the anti-inflammatory effects of corticosteroids. Here, we investigate the contribution of the SIRT1 single-nucleotide polymorphisms (SNPs) rs12778366 and rs4746720 to ITP susceptibility.MethodsWe recruited 330 ITP patients and 309 healthy controls from Han population, and performed genotyping of SIRT1 rs12778366 and rs4746720 using a MassARRAY system. The results were validated in another 55 ITP patients from ethnic minorities.ResultsUsing clinical data of patients and controls from Han polulation, including corticosteroid sensitivity, susceptibility, refractoriness, and severity, our results revealed that the CC/TC genotypes of SIRT1 rs12778366 were associated with a 2.034-fold increased risk of corticosteroid resistance compared to the homozygous major TT genotype (dominant, CC/TC vs. TT, OR = 2.034, 95% CI = 1.039–3.984,p= 0.038). In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a 0.560-fold decreased risk of corticosteroid resistance (dominant, 95% CI = 0.321–0.976, OR = 0.560,p= 0.041). The C allele substitute in SIRT1 rs12778366 was significantly associated with the corticosteroid sensitivity of ITP patients (p= 0.021). The similar results were obtained in minority ITP patients.ConclusionThis study indicates that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.