DETERMINATION OF THE RELATIONSHIP BETWEEN GENE POLYMORPHISMS ENCODING IMMUNE REGULATORY CYTOKINES AND INHIBITOR DEVELOPMENT IN PATIENTS WITH SEVERE HEMOPHILIA A
Project no. 20176 · Status: Kapanmış · 2018
Summary
Objective: The development of neutralizing antibodies against infused factor VIII called inhibitor is the most challenging treatment complication in hemophilia A (HA) patients. In this study, we aimed to analyze the association between three variants in two genes (c.-318C>T; rs5742909 and c.49A>G; rs231775 in CTLA-4 and c.-308G>A; rs1800629 in TNF-?) and inhibitor development in a cohort of severe HA patients with intron 22 inversion mutation. Method: The study included in 94 severe HA patients with intron 22 inversion. Two groups were established according to the inhibitor status: inhibitor positive and inhibitor negative. We investigated two SNPs in CTLA-4 (c.-318C>T; rs5742909 and c.49A>G; rs231775) and one in TNF-? (c.-308G>A; rs1800629) using Sanger sequencing in both groups. Results: All 94 severe HA patients included in the study were male. It was evaluated as inhibitor positive in 25 patients (26.6%) and inhibitor negative in 69 patients (73.4%). In this study, no significant correlation between CTLA-4 polymorphisms and inhibitor development was observed in severe HA patients with intron 22 inversion mutation. However, the A allele for c.-308G>A variant in TNF-? was found to be associated with the increased risk for inhibitor development in those patients. Conclusion: In Turkish patients with severe HA with intron 22 inversion mutation, when genetic risk factors are examined, c.-318C>T and c.49A>G variants in the CTLA-4 gene are not associated with inhibitor development, while the A allele for c.-308G>A variant in the TNF-? is related to the risk of inhibitor development.