Investigating the IGSF2 and TNFα Genes Polymorphism and the Risk of Inhibitor Development in Patients with Hemophilia A

Abstract

Background and purpose: Hemophilia is a hereditary X-linked disorder. Females are carriers and males have the disorder. Hemophilia A is caused by deficiency in the production of factor VIII. In some hemophilia patients, inhibitors including IgG1 and IgG4 antibodies are expressed against this factor. These inhibitors interact with factor VIII and suppress its function. The current study aimed at investigating the relationship between single nucleotide IGSF2 and TNFα genes polymorphism and development of inhibitors in patients with hemophilia A. Materials and methods: In this case-control study, 100 patients with hemophilia A were selected (55 with inhibitor and 45 without inhibitor). Recognition of inhibitor was performed by Bethesda test. DNA was extracted from whole blood samples. A single-nucleotide polymorphism of IGSF2 and TNFα genes was performed using Tetra ARMS-PCR assay. Results: Hardy-Weinberg equilibrium was investigated in both groups. Comparing the IGSF2 and TNF-α genotypes in these groups indicated a significant correlation between single-nucleotide polymorphism of IGSF2 and development of inhibitors (p= 0.018, odds ratios for AA and AG genotypes were 1.39 and 0.37, respectively). A significant association was seen between incidence of inhibitors and consanguineous marriages and viral infection (p<0.05). Moreover, the association between response to treatment and Bethesda test was significantly different between the two groups (p= 0.002). Conclusion: According to these results, the risk of development of inhibitors has a direct relationship with mutation in IGSF2 gene.

Keywords

• hemophilia a
• inhibitor
• polymorphism
• igsf2 gene
• tnf-α gene