Identification of candidate genes involved in clinical variability among Tunisian patients with β-thalassemia

The short tandem repeats (STR) are undoubtedly the most used molecular markers in genetic diversity studies. β-thalassemia is a hereditary hemolytic anemia which is a common health problem all over the world. The disease has two main clinical forms: the severe form or β-thalassemia major (TM) and the moderate form or β-thalassemia intermedia (TI). To help understand this inconsistency, five STR have been studied in a group of 27 β-thalassemic patients divided into 15 (TM) and 12 (TI). For each STR, the distribution of alleles, has been compared among patients with β-thalassemia major (TM) and those with β-thalassemia intermedia (TI).The comparison has shown, for the STR D14S72, one specific allele to (TM) and for the STR D14S990 and D14S68, two specific alleles to TI patients. The combination of these alleles with severe beta-thalassemia genotypes leads to the phenotype of beta-thalassemia intermedia even though there are no any attenuating factors such as XmnI Gg polymorphism at position -158 of the HBG2 promotor or the alpha-globin defects. This suggests that these alleles are associated with factors reducing β-thalassemia clinical effects. One of this STR is located in the 5'UTR of the CEBPε gene which incodes a transcription factor expressed in the myeloid lineage. Thus, the involvement of the transcription factor CEBPε in the myeloid cells suggests that CEBPε is a candidate gene involved in the modulation of the β-thalassemia expression through immune system reactions.