Factor VIII inhibitors and tumor necrosis factor-α-308 gene polymorphism in a Cohort of Egyptian children with Hemophilia A

Background Correlation of the phenotypic and genotypic characteristics of hemophilia A (HA) children with inhibitor development can improve significantly disease management. Objectives We aim to investigate the potential association between the clinical phenotypes of HA, factor VIII inhibitor development, and polymorphisms of tumor necrosis factor-α (TNF-α)-308 in a cohort of pediatric Egyptian patients with HA. Patients and methods Clinical data and blood samples were collected from 95 HA patients to screen for inhibitor development using the Bethesda assay. Also, a case–control study comprising 45 HA patients and 45 controls was conducted to analyze TNF-α-308 gene polymorphism by using PCR-restrictive fragment length polymorphism. Results The prevalence of factor VIII inhibitors among our patients was 28.4% (27/95). Out of 27 patients positive for inhibitors, 19 (70%) were low responders, while eight (30%) were high responders. Independent predictors for high titer inhibitors were found to be severe HA, positive family history of hemophilia, and less than 50 days duration between exposure days. As regards TNF-α-308 gene polymorphism, the difference in the genotype frequencies between HA patients and controls was nonsignificant. Further, the genotype frequencies revealed no statistically significant difference between the inhibitor-positive and inhibitor-negative groups. Conclusion Clinical phenotypes of positive inhibitors and high titer inhibitor HA patients in our ethnicity were defined. However, inhibitor formation among our patients was not found to be related to TNF-α-308 gene polymorphism.