Effect of CTLA-4 and TNF-α Gene Polymorphisms on Inhibitor Development in a Turkish Cohort of Severe Hemophilia A Cases with Intron 22 Inversion Mutation: An Analytical Study

Objective: The development of neutralizing antibodies against infused factor VIII called inhibitor is the most challenging treatment complication in hemophilia A (HA) patients. Associated factors for are classified into 2 groups (genetics and non-genetics). Genetic other than mutation type F8 gene include family history, ethnical origin, human leucocyte antigen haplotype, a number polymorphisms genes which play role immune system. In this study, we aimed to analyze association between 3 variants [c.-318C>T; rs5742909 c.49A>G; rs231775 CTLA-4 c.-308G>A; rs1800629 tumor necrosis alpha (TNF-α)] cohort severe HA patients with intron 22 inversion (inv22) mutation. Material Methods: study included 94 inv22. Two were established according status: positive negative. We investigated single nucleotide (c.- 318C>T; rs231775) one TNF-α (c.-308G>A; rs1800629) using Sanger sequencing both groups. Results: no significant relationship was observed inv22 However, allele c.-308G>A variant found be associated increased risk those Conclusion: Turkish mutation, c.-318C>T c.49A>G not development, whereas TNF-α, related development.