الفهرس 
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Abstract
Hemophilia A is an X-linked recessive bleeding disorder caused by the deficiency or abnormality of factor VIII coagulant activity. Administration of factor VIII concentrates prepared from plasma or produced by recombinant DNA technology, is used to treat or prevent bleeding. An important complication in patients with severe hemophilia is the development of alloantibodies that block the activity of the relevant factor (inhibitors). These inhibitory antibodies develop in response to exogenous factors. The formation of a FVIII inhibitor is a T-cell dependent event that includes antigen-presenting cells and B- and T-helper lymphocytes .Inhibitors complicate bleeding episodes because they decrease responsiveness to factor infusions. Multiple research studies have shown that people with certain types of hemophilia gene mutations are more likely to develop an inhibitor
Many cytokines polymorphism, including TNF-α may affect inhibitor development. The aim of this study was to investigate the relation between TNF-α gene promotor polymorphism at position (−308 G<A) and susceptibility of patients with hemophilia A to develop factor VIII inhibitors.
Patients were screened for FVIII inhibitors using the Bethesda method. TNF-α (-308 G<A) polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism.
The results revealed that 8 hemophilic patients (16%) developed inhibitors to factor VIII with factor activity ranged between 0.2-4.9 IU/ml while patients who didn’t develop inhibitors were 42 patients (84%), with factor activity ranged between 0.9-2.5 IU/ml.
The incidence of G allele was 53% while incidence of A allele was 47 %. GA bi-allelic SNP was in 45 patients, GG in 4 patients and AA in 1 patient.
Among inhibitor group, the frequency of G allele was 56.3 % while A allele was 43.8%. The frequency of GA SNP was 87.5 %, GG was 12.5% and AA was 0%., while among non-inhibitor group, the frequency of A allele was 47.6% while G allele was 52.4%. The frequency of GA SNP was 90.5%, GG 7.1% and AA was 2.4%.
By this results there was no statistically significant difference found between inhibitor positive and negative patients regarding TNF-α (-308 G<A) genotypes, disease severity, or treatment-related variables (p=1).
FVIII inhibitor formation in this group of Egyptian hemophiliacs was not correlated to TNF-α (-308 G<A) polymorphism, disease severity, or any of the treatment variables.
Keywords: Egypt; FVIII inhibitors; Hemophilia A; TNF-α gene polymorphism