First description of the rs45496295 polymorphism of the C/EBPE gene in β-thalassemia intermedia patients. (1st November 2016)

• Record Type: Journal Article
• Authors: Mejri, Awatef; Mansri, Marwa; Hadj Fredj, Sondess; Ouali, Faida; Bibi, Amina; Hafsia, Raouf; Messaoud, Taieb; Siala, Hajer
• Is Part Of: Hemoglobin. Volume 40:Number 6(2016)
• Page Start: 411
• Page End: 416
• Publication Date: 2016-11-01
• Subjects: β-Thalassemia intermedia -- C/EBPE gene -- clinical modulation -- hemolysis -- rs45496295 (C > T) polymorphism; Hemoglobinopathy -- Periodicals; Hemoglobin -- Periodicals; Hematology -- Periodicals; Thalassemia -- Periodicals; Blood -- Diseases -- Periodicals; 612.1111
• DOI: 10.1080/03630269.2016.1252386
• Languages: English
• ISSNs: 0363-0269

Abstract

Abstract: The C/EBPE gene, located in 14q11.2, encodes for a B/zip-type transcription factor. The C/EBPɛ is involved in terminal differentiation and functional maturity of granulocyte progenitor cells and in cell apoptosis during myeloid differentiation. A C/EBPE gene has recently been described as a candidate gene involved in clinical variability of β-thalassemia (β-thal). In this study, the C/EBPE gene was sequenced in 146 subjects divided into the severe type of β-thal major (β-TM) and moderate type of β-thal intermedia (β-TI), and a control group. The analysis identified the rs45496295 (C > T) polymorphism in the heterozygous state in 73.9% β-TI patients, which was not the case in the β-TM patients or in the control group. Thus, the T allele is consequently associated with the β-TI group ( p = 10 −3 ). According to the Human Splicing Finder (version 3.0, Marseille, France), the presence of the rs45496295 polymorphism leads the creation of a new intronic exotic splicing enhancer (ESE) site. Moreover, the T allele of rs45496295 is associated with a lower transfusion regimen ( p = 10 −3 ) and a higher pretransfusion hemoglobin (Hb) rate ( p = .006). The comparison of several factors concerning T allele carriers and non-carriers showed that the T allele does not act on the Hb F rate. The T allele of rs45496295, associated with moderate type of β-thal, seems to modify the C/EBPɛ action, thereby preventing the hemolysis.