PB0171 - Polymorphisms in MAPk9 and CSF1R Associated with Immune Regulatory Gene and their Impact on Inhibitor Development in Patients with Hemophilia A

Background: The most serious disaster of substitution therapy in hemophilia A (HA) patients is the development of inhibitors to infused factor VIII. As a result, these patients have much lower quality of life due to recurrent bleeding episodes, an incapacitating arthropathy, and a shortened life span. Immune compromised genes have been found to be the most important risk factor among several others and may play a significant influence in the development of inhibitor.

Aims: The purpose of this study was to assess how two single nucleotide polymorphisms SNPs in an immune regulatory system affected the development of inhibitors.

Methods: Taken approval from Institutional Review Board of concerned institute. Similarly, after taken an informed consent sample were collected. This study encompasses on 200 cases and controls. Total 100 HA patients were enrolled, among 60 severe inhibitors negative, 10 severe inhibitor positive and 30 mild/moderate. Genomic DNA was extracted followed by primer designing through primer.1 software. T-ARMs-PCR was designed for gene amplification and observed on electrophoresis.

Results: Results showed protective significant association of (rs4147385, G< A) and (rs10079250, A< G) in inhibitor production of hemophilia A patients. The homozygous wild GG with 71% was found as major allele and homozygous variant AA with 29% as minor in MAPK9, (OR=0.0355, 95% CI= 0.015-0.083, P =0.001) while homozygous wild AA with 55% was found as major and homozygous variant GG with 45% as minor in CSF1R, (OR=0.006, 95% CI= 0.090-0.726, P < 0.001) in cases.

Conclusion(s): Currently the available treatment for HA inhibitor is substandard, therefore the major focus of HA research has been figuring out the risk factors that may involve in inhibitor development and optimal regime strategies to overcome this issue. This study was concluded that significance association have been observed in targeted genes without causing any negative effect in inhibitor production in severe hemophilia A patients.