HDAC3 single-nucleotide polymorphism rs2530223 is associated with increased susceptibility and severity of primary immune thrombocytopenia

Abstract

Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by a low platelet count and increased risk of bleeding. We previously reported that low-dose chidamide, a histone deacetylase (HDAC) inhibitor, restores immune tolerance in patients with ITP. This study aimed to evaluate the association of a single-nucleotide polymorphism (SNP) rs2530223 in the HDAC3 gene with susceptibility to ITP and its clinical features.

Methods: Patients with ITP and age-matched healthy participants were recruited for this case-control study. Genotyping of the HDAC3 rs2530223 polymorphism was performed using MassARRAY platform.

Results: Individuals with T allele of HDAC3 rs2530223 exhibited a 1.472-fold increased risk of ITP susceptibility (OR 1.472; 95% CI 1.100-1.969; p = .009), while ones with the TT genotype under the codominant and recessive models, and the TC/TT genotypes under the dominant model all revealed increased risk of ITP susceptibility (dominant odds ratio[OR] 1.965; 95% CI: 1.046-3.656; p = .036; codominant OR 2.264; 95% CI 1.175-4.360; p = .015; and recessive OR 1.512; 95% CI 1.028-2.224; p = .036, respectively). Regarding platelet counts in ITP patients, we observed that the TC/TT genotypes exhibited a 3.932-fold increased risk for platelet (PLT) <30 × 10⁹ /L (OR 3.932; 95% CI 1.426-10.842; p = .008).

Conclusion: This study indicates that HDAC3 rs2530223 may be an important genetic factor related to ITP susceptibility and platelet count in ITP patients, providing new perspectives on disease progression, new therapeutic targets, and severity prediction.

Keywords: HDAC3; platelet count; primary immune thrombocytopenia; single-nucleotide polymorphism; susceptibility.