The Role of BCL11A and HBS1L-MYB Polymorphisms in Predicting Blood Transfusion Requirements of Thalassemia Patients with Homozygous 5 HS4-LCR/Xmn1-HBG2 Background

Our previous studies on thalassemia patients, homozygous or compound heterozygous for severe beta thalassemia mutations, has suggested that 5’HS4-LCR and/or Xmn1-HBG2 backgrounds, which were linked in our thalassemia patients, are important in determining the blood transfusion dependency of these individuals. While the majority of patients with AA/-- 5’HS4/Xmn1 background, were severely dependent on blood transfusion, a considerable variation in blood transfusion requirement was observed among patients with GG/++ background. To investigate other factors that could explain this diversity among GG/++ patients, 2 BCL11A together with 2 HBS1L-MYB SNPs, associated with HbF levels in GWAS, were genotyped. Five groups of patients with specific genotypic patterns for these SNPs were identified. However, a similar distribution pattern of phenotypes was observed in all groups, ranging from extremely mild to severe. These preliminary results indicate that the heterogeneity observed in the phenotype of patients with the same background for 5’HS4-Xmn1, could not be explained by the difference in BCL11A and/or HBS1L-MYB SNPs in this study. Therefore these SNPs alone, could have limited value in terms of clinical decision making.