Determination of HSP90B1 polymorphisms as genetic risk factors for inhibitors in Iranian hemophilia A patients

Background: Hemophilia A (HA) is an X-linked bleeding disorder in which the deficiency of factor VIII (FVIII) results in problems with hemostasis. Antibodies, also called inhibitors, are high-affinity immunoglobulin G (IgG) that are directed against infused FVIII; this reduces the effectiveness of treatmen. The aim of the present study was to analyze the relationship between inhibitor development and HSP90B1 gene polymorphisms in HA patients from Iran.Materials and Methods: Seventy hemophilia A patients were selected to determine the presence of inhibitor using Bethesda test. Extraction of genomic DNAs from blood samples was performed. Then, primer1 software was used to design primers for Tetra ARMS-PCR. The validation of SNPs in HSP90B1 gene was determined using DNA sequencing. Finally, statistical analysis of polymorphisms was done by chi squared test.Results: Genotyping of HSP90B1 gene in 70 HA samples (with and without inhibitors) revealed that there was no deviation from Hardy-Weinberg equilibrium (p = 0.474, OR = 1.680, CI = 0.405-6.962 for AG and p= 0.961, OR = 1.032, CI = 0.296-3.590 for GG genotype, respectively). The analysis of polymorphisms in alleles of the HSP90B1 gene of HA patients identified no association between alleles and the risk of inhibitors (p > 0.05).Conclusion: Our data indicated that polymorphisms in HSP90B1 gene cannot be suggested as a genetic risk factor for development of inhibitors in Iranian HA patients.

کلیدواژه ها:

Polymorphism ، Inhibitor ، Hemophilia A ، Tetra Primer Arms PCR ، HSP90B1