Banan Mehdi, Bayat Hadi, Azarkeivan Azita, Mohammadparast Saeid, Kamali Koorosh, Farashi Samaneh, Bayat Nooshin, Khani Masumeh Hadavand, Neishabury Maryam, Najmabadi Hossein
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Hemoglobin. 2012;36(4):371-80. doi: 10.3109/03630269.2012.691147. Epub 2012 Jun 11.
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.
羟基脲（HU）是一种能够重新激活胎儿血红蛋白（Hb F）生成的药物，常用于给β地中海贫血（β-地贫）患者开药。然而，只有一部分患者在接受HU治疗后输血需求会减少。由于其潜在的副作用，必须有针对性地开具HU处方。为了确定与药物反应相关的基因标记，我们对81名依赖输血的伊朗β-地贫患者进行了一项回顾性关联研究，研究三个Hb F数量性状位点（QTL）中的单核苷酸多态性（SNP）：XmnI多态性、BCL11A以及HBS1L-MYB基因间区域，与对HU的反应。治疗后输血间隔时间的增加用于衡量药物反应。我们的结果表明，XmnI T/T基因型或BCL11A rs766432 C等位基因的存在与对HU的反应密切相关（p<0.001）。因此，这些标记可用于准确预测伊朗β-地贫患者对HU的反应。
