First description of the rs45496295 polymorphism of the C/EBPE gene in β-thalassemia intermedia patients.

The C/EBPE gene, located in 14q11.2, encodes for a B/zip-type transcription factor. The C/EBPe 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 beta-thalassemia ( beta-thal). In this study, the C/EBPE gene was sequenced in 146 subjects divided into the severe type of b-thal major ( beta-TM) and moderate type of beta-thal intermedia ( beta-TI), and a control group. The analysis identified the rs45496295 ( C> T) polymorphism in the heterozygous state in 73.9% beta-TI patients, which was not the case in the b-TM patients or in the control group. Thus, the T allele is consequently associated with the beta-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 beta-thal, seems to modify the C/EBPe action, thereby preventing the hemolysis.