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

Background: Primary 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.

Methods: We 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.

Results: Using 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.

Conclusion: This study indicates that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.