The XmnI (G)gamma polymorphism influences hemoglobin F synthesis contrary to BCL11A and HBS1L-MYB SNPs in a cohort of 57 beta-thalassemia intermedia patients.

The HbF level is a quantitative trait influenced by many loci inside or outside the beta-globin gene cluster. The aim of this study was to analyze in 57 beta-thalassemia intermedia patients with very various genotypes the effects on fetal hemoglobin levels of SNPs lying in three genes or chromosome regions which include the XmnI (G)gamma polymorphism at position -158 of the HBG2 promoter (rs7482144), two SNPs located in the BCL11A region (rs4671393 and rs11886868) and three SNPs located in the HBS1L-MYB region (rs28384513, rs9399137 and rs4895441). Our study shows a strong correlation between the XmnI (G)gamma polymorphism and the fetal hemoglobin expression in this patient population (p=0.002). Unfortunately, although recent studies clearly showed a role of SNPs in BCL11A and a HBS1L-MYB region on either clinical expression or fetal hemoglobin levels of beta-hemoglobinopathies such as sickle cell disease and beta-thalassemia, SNPs in BCL11A and the HBS1L-MYB region did not show statistically significant correlations with fetal hemoglobin levels. This suggests that the BCL11A and HBS1L-MYB loci have a minor effect on HbF level compared to the XmnI QTL in beta-thalassemia intermedia patients. 2010 Elsevier Inc. All rights reserved.