The XmnI andBCL11ASingle 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.

Modifying effect of XmnI, BCL11A, and HBS1L-MYB on clinical appearances: A study on β-thalassemia and hemoglobin E/β-thalassemia patients in Indonesia

“…The combination of these alleles has a determinant value of 10.7% against HbF changes in HbE/bthal patients. Similar findings were reported by Banan et al [47] who reported that the +CC allele for XmnI, rs766432, and rs9399137 showed a good response to changes in HbF in patients with thalassemia intermedia receiving hydroxyurea supplementation. In addition, the combination of alleles +CCC contributed to increase HbF levels (about 17.5%) among SCD patients in African populations [48].…”

Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

“…T G g) was a strong predictor of favorable responses, 44,72,75,79,80,97 although the case was different in some studies, especially those including patients with hemoglobin E/b-thalassemia. 65,68,70,77 A 2012 study 97 also showed that the rs766432 polymorphism at intron 2 of the BCL11A gene correlates strongly with a response to hydroxyurea therapy; further studies in this direction are encouraged. However, it is important to bear in mind that when genetic markers are studied, the markers themselves may not be causally linked to such effects, but rather variants in linkage disequilibrium with these markers may be the mediators of such effects.…”

Study on Hydroxyurea Response in Hemoglobinopathies Patients Using Genetic Markers and Liquid Erythroid Cultures

“…rs11886868 and rs4671393) with higher HbF levels in patients with hemoglobinopathies. 12,14 In particular, a strong association between rs11886868 and HbF level was highlighted in the Sardinian population. 15 High HbF levels have been also associated with rs4671393 SNP (A/A genotype) in two different SCD cohorts (African American Cooperative Study of Sickle Cell Disease and SCD cohort from Brazil).…”