title: Effect of Cis Acting Potential Regulators in the β Globin Gene Cluster on the Production of HbF in Thalassemia Patients.
abstract: The clinical presentation of β-thalassemia intermedia phenotypes are influenced by many factors. The persistence of fetal hemoglobin and several polymorphisms located in the promoters of γ- and β-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 β-thalassemia carriers, β-thalassemia intermedia, β-thalassemia major and normal controls of Indian origin. The -158 Gγ T allele was found to be associated with increased levels of HbF in β 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 β globin cluster, whether in cis or in trans to each other, can interact to enhance HbF expression when a β thalassemic determinant is present in heterozygosity and help in amelioration of the severity of the disease in homozygotes.
authors.affiliation: National Institute of Immunohaematology (ICMR), 13th Floor, New Multistoried Building, K.E.M. Hospital Campus, Parel, Mumbai -4000 12.
authors.forename: Pooja
authors.initials: P
authors.lastname: Dabke
authors.forename: Roshan
authors.initials: R
authors.lastname: Colah
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Anita
authors.initials: A
authors.lastname: Nadkarni