Screening association between gamma-globin promoter region mutation and hemoglobin F, among patients with beta-thalassemia majör in Antalya

Objective: Beta thalassemia is one of the single gene diseases with autosomal recessive inheritance and one of the most common hemoglobinopathies in our country and Antalya Province as well as in the world and. The purpose of this study is to screen the mutations in the promoter of the G-Gamma and A-gamma globin genes, which are thought to cause the increase of HbF and are found in the HbF structure, by binding some transcription factors while in the mutant form in adulthood, in beta thalassemia major patients, which are common in Antalya, Turkey and to reveal the relationship with the height of HbF. Method: In the study, after DNA extraction from peripheral blood in 30 beta-thalassemia major patients with high HbF and 30 healthy individuals without thalassemia, the G-gamma and A-gamma promoter region was amplified by polymerase chain reaction (PCR) using target-recognizing the pair of primers. PCR products were sequenced by Sanger DNA sequencing method and screened for mutations. Findings were evaluated as percentages. Results: Since successful results were obtained in 27 of 30 beta-thalassemia major patients with high HbF in this study, 3 patients with no results were not included in the calculations. In terms of mutant alelle distribution, the most frequent allele was IVS.I.110 (G>A) with %75,92 of frequency. IVS.I.110 (G> A) /IVS.I.110 (G> A) homozygous genotype was found in 17 patients. G-gamma and A-gamma promoter regions of both patients and 30 healthy control individuals were found to be in normal genotype. Conclusion: In our study, the G-gamma and A-gamma promoter regions were screened the first time for mutations and found to be in normal genotype in beta thalassemia major patients with high HbF in Antalya Province, Turkey. These promoter regions contain sequence motifs at the target of many transcription factors, especially TAL1, in the regulation of HbF. Although these regions were normal, it was considered an important finding in terms of being the new target of other factors acting together with TAL1 in elevated HbF in patients. Keywords: Thalassemia major, Hb F elevation, Gamma globin, promoter region, mutation