The Impact of the Rs3806596; T>C Genetic Polymorphism of UDP Enzyme on the Response to Deferasirox Drug Among Iraqi Thalassemia Patients

Abstract

Background: thalassemia is an autosomal recessive hereditary condition, Patients with beta thalassemia need ongoing blood transfusions and iron chelating treatment due to the body's inability to excrete iron. Clinical observations of transfusion dependent thalassemia (TDT) patients in the local community show that many of them continue to have elevated blood ferritin levels even after receiving treatment with the iron chelator Deferasirox (DFX). One of the primary UGT1 enzyme families that metabolizes DFX is the UDP-glucuronosyltransferase 1A3 (UGT1A3) gene. This study examines the impact of the UGT1A3 gene's rs3806596; T>C single nucleotide polymorphism (SNP) on Iraqi TDT patients' clinical response to DFX chelation treatment.

Methodology: Cross-sectional study included 96 TDT patients of Iraqi male and female.They were administered with 30–40 mg/kg of oral DFX daily for at least 3 months, and they ranged in age from 8 to 39. Serum erythroferrone, liver and kidney function tests, and serum ferritin were evaluated. The method of allele-specific polymerase chain reaction was used to identify the rs3806596; T>C SNP.

Results: The genotype distribution of rs3806596; T>C SNP among Iraqi population was 36.5%, 18.5% and 44.8%, for TT, TC and CC respectively. The frequency of the wild (T) allele is 0.46, compared to 0.54 for the mutant (C) allele. The mutant group (CC) of rs3806596; T>C SNP showed no significant in the three different groups.

Conclusion: There is no significant association between rs3806596; T>C SNP of the UGT1A3 gene and the therapeutic response to DFX in our samples of Iraqi population for TDT patients.