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

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.