The XmnI and BCL11A Single Nucleotide Polymorphisms May Help Predict Hydroxyurea Response in Iranian β-Thalassemia Patients

Abstract

Hydroxyurea (HU), a drug which can reactivate fetal hemoglobin (Hb F) production, is frequently prescribed to β-thalassemia (β-thal) patients. However, transfusion requirements of only a subset of patients are reduced upon HU treatment. Because of its potential side-effects, targeted prescription of HU is imperative. To identify genetic markers that correlate with drug response, we have carried out a retrospective association study of single nucleotide polymorphisms (SNPs) in three Hb F quantitative trait loci (QTLs): the XmnI polymorphism, BCL11A, and the HBS1L-MYB intergenic region, with the response to HU in a cohort of 81 transfusion-dependent Iranian β-thal patients. An increase in blood transfusion intervals post-therapy was used to measure drug response. Our results suggest that presence of the XmnI T/T genotype or the BCL11A rs766432 C allele correlates strongly with response to HU (p <0.001). Accordingly, these markers may be used to accurately predict the HU response of Iranian β-thal patients.

• β-Thalassemia (β-thal)
• Hydroxyurea (HU)
• BCL11A Single nucleotide polymorphism (SNP)
• XmnI Polymorphism

ACKNOWLEGMENTS

We thank Dr. Sjaak Philipsen (Erasmus Medical Center, Rotterdam, The Netherlands) for his critical comments on the manuscript. This study was supported by the Genetics Research Center (University of Social Welfare and Rehabilitation Sciences, Tehran, Iran) grant 64032 to Mehdi Banan.