Polymorphism analysis of the CTLA-4 (rs231775) gene as a marker of inhibitor development in Iranian patients with hemophilia A

Development of factor VIII (FVIII) inhibitor is the main problem of replacement therapy in patients with hemophilia A. Recently, the correlation of polymorphisms of some genes involved in immune system has been determined with inhibitor development. The reports showed that cytotoxic T lymphocyte antigen-4 (CTLA-4) plays an important role in regulating T cell activation and thus, CTLA-4 gene polymorphism is related to genetic susceptibility to various autoimmune diseases. This study aimed at investigating the correlation between polymorphism of CTLA-4 gene and inhibitor development in Iranian hemophilia A patients for the first time.
In this case-control study, the genomic DNA was extracted from blood samples of 55 inhibitor positive and 45 inhibitor negative hemophilia A patients. Then, the genotyping of the CTLA-4 gene was performed using the Tetra Primer ARMS PCR. Moreover, the validation of single nucleotide polymorphisms (SNPs) in the CTLA-4 gene was determined by DNA sequencing. On the other hand, the role of HCV infection was determined in inhibitor-positive and inhibitor-negative HA patients.
Results showed that no statistically significant difference was observed between the genotypic and allelic frequencies with the presence of inhibitors (P>0.05). Moreover, a significant correlation was observed between HCV infections and development of inhibitors (P The CTLA-4 gene polymorphism does not play a role for inhibiting coagulation factor in Iranian patients with hemophilia type A.