Jornal de Farmacogenômica e Farmacoproteômica

Abstrato

Factor 8 Gene Mutations and Risk of Inhibitor Development in Hemophilia A Algerian Patients

Faouzia Zemani-Fodil, Meriem Abdi, Mostefa Fodil, Meriem Samia Aberkane, Naima Mesli, Mohamed Belazaar, Malika Mehalhal, Yasmina Rahal, Hadj Touhami, Nadhira Saidi-Mehtar and Abdallah Boudjema

Background: Neutralizing inhibitors development toward factor VIII is one of the most challenging complications in the treatment of hemophilia A. Several studies have suggested that genetic factors influence the development of factor VIII inhibitors such as ethnicity, family history, mutations in the factor 8 gene and in genes of the immune system. The aim of the present study was to analyze the relationship between inhibitor development and F8 gene mutation types in a sample of hemophiliac patients from West Algeria.

Methods: To study the molecular predisposition for inhibitor development, we genotyped 24 hemophiliac patients with and without inhibitors. A conventional Fisher’s exact test was used for statistical analysis. A p-value<0.05 was considered to indicate statistical significance.

Results: A total of seven patients had developed inhibitors, while seventeen had not. Six patients with inhibitors (86%) were classified as low responder; whereas, one patient (14%) was categorized as high responder with the Bethesda inhibitor level above five unit.

Among the inhibitor-positive patients, we identified 4 with intron 22 inversion, 1 with a nonsense mutation (c.322A > T, p.Lys108*) and 2 without an identified F8 mutation.

We showed that there was any association of the F8 gene mutations and the inhibitor development in our studygroup. However, these findings should be confirmed in a larger group of patients.

In conclusion, genetic factors are not the only determinant of inhibitor development in HA; environmental factors play an important role.