Effect of cis acting potential regulators in the ß globin gene cluster on the production of HbF in thalassemia patients

Abstract

The clinical presentation of ß-thalassemia intermedia phenotypes are influenced by many factors. The persistence of fetal hemoglobin and several polymorphisms located in the promoters of γ- and ß-globin genes are some of them. The aim of this study was to evaluate the combined effect of the -158 Gγ (C→T) polymorphism and of the (AT)x(T)y configuration, as well as their eventual association with elevated levels of HbF in ß-thalassemia carriers, ß-thalassemia intermedia, ßthalassemia major and normal controls of Indian origin. The -158 Gγ T allele was found to be associated with increased levels of HbF in ß thalassemia carriers, and not in wild-type subjects. In the homozygous group, the -158 Gγ T allele was significantly higher in the thalassemia intermedia group (66%) as against the thalassemia major group (21%). The (AT)9(T)5 allele did not show any association with raised HbF levels. However 24% of milder cases showed presence of this allele. This study suggests that two regions of the ß globin cluster, whether in cis or in trans to each other, can interact to enhance HbF expression when a ß thalassemic determinant is present in heterozygosity and help in amelioration of the severity of the disease in homozygotes.