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/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.
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Awatef
A
Mejri
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Marwa
M
Mansri
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Sondess
S
Hadj Fredj
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Faida
F
Ouali
b Biochemistry Laboratory , National Institute of Nutrition and Food Technology , Tunis , Tunisia.
Amina
A
Bibi
c Hematology Department , Hospital Aziza Othmana , Tunis , Tunisia.
Raouf
R
Hafsia
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Taieb
T
Messaoud
a Biochemistry and Molecular Biology Laboratory , Children's Hospital Bechir Hamza, Research Laboratory LR00SP03 , Tunis , Tunisia.
Hajer
H
Siala
D000328:Adult; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017086:beta-Thalassemia / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; D006454:Hemoglobins; C070790:CEBPE protein, human; D005319:Fetal Hemoglobin
C/EBPE gene; clinical modulation; hemolysis; rs45496295 (C > T) polymorphism; β-Thalassemia intermedia