The XmnI and BCL11A single nucleotide polymorphisms may help predict hydroxyurea response in Iranian β-thalassemia patients.
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.
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. mbbanan@yahoo.com
Mehdi
M
Banan
Hadi
H
Bayat
Azita
A
Azarkeivan
Saeid
S
Mohammadparast
Koorosh
K
Kamali
Samaneh
S
Farashi
Nooshin
N
Bayat
Masumeh Hadavand
MH
Khani
Maryam
M
Neishabury
Hossein
H
Najmabadi
D000328:Adult; D000986:Antisickling Agents / Q000627:therapeutic use; D001803:Blood Transfusion; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007492:Iran; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy
D000986:Antisickling Agents; D005319:Fetal Hemoglobin; D006918:Hydroxyurea