الفهرس 
?-Thalassemia.Only 14 pages are availabe for public view
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Abstract
β-Thalassemia is a genetic disorder that results from β-globin gene mutations leading to defective synthesis of adult hemoglobin (Hb A).
Clinical consequences vary tremendously from nearly asymptomatic to severely anemic and transfusion dependent patients.
Phenotypic variations have been linked, not only to the type of β-globin gene mutations and amount of synthesized Hb A, but to recently discovered genetic modifiers mapping outside the β-globin gene cluster including BCL11A gene polymorphism. These modifiers are associated with increased Hb F levels.
This studty aimed to investigate the impact of SNP rs11886868 in the BCL11A gene on clinical status of Egyptian β-thalassemia patients.
The study included 120 β-thalassemia children and adolescents (71 males and 49 females), with mean age of 8.59 year, who attended the Pediatric hematology unit and laboratory in Menoufia University Hospitals suffering from anemia or for blood transfusion.
Full history taking, clinical assessment and clinical scoring of thalassemia severity by phenotypic scoring system proposed by Nadkarni et al., 2007 were done.
Blood samples were collected from patients before transfusion of blood to perform complete blood count (CBC) and reticulocytic count, serum bilirubin, ferritin levels, quantitative measurement of different hemoglobin types by high performance liquid chromatography (HPLC) and analysis of single nucleotide polymorphism (SNP) rs11886868 in the BCL11A gene by Taqman SNP genotyping assay and Real Time PCR.
This study has shown lower frequency of the CC genotype and C allele. The TT genotype and T allele were more common among Egyptian β-thalassemia patients.
The relation between BCL11A (rs11886868) genotypes and total baseline hemoglobin levels was non-significant. However, the BCL11A (rs11886868) had statistically significant associations with Hb F levels.
To accurately describe Hb F levels, the mere Hb F percentage values were not included (notice that in a patient with markedly low/absent Hb A production, Hb F percentage can be very high. This may be misleading because the actual Hb F production may be low). Instead, Hb F levels (in g/dl) were stratified according to the levels of total Hb and levels of Hb A.
The Hb F levels when normalized to total Hb levels and to Hb A levels were significantly higher in patients with the CC genotype followed by patients with CT genotype and was the lowest in patients with TT genotype.
Based on total baseline hemoglobin levels, patients were categorized into patients with Hb < 5 g/dl, 5- <8 g/dl and ≥ 8 g/dl. In each of these groups, Hb F levels showed highly significant and significant differences among different BCL11A genotypes.
Similarly, patients were grouped based on hemoglobin A levels into patients with hemoglobin A 0- < 4 g/dl, 4- < 6 g/dl and ≥ 6 g/dl. Hemoglobin F levels showed highly statistical significances among different BCL11A genotypes at different hemoglobin A levels.
Summary
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All cases of CC genotype had phenotypic score of ≤ 8 that correspond to thalassemia intermedia while most cases of TT genotype had score of ˃ 8 that correspond to thalassemia major with highly significant P value
˂ 0.001. Hence, CC genotype is associated with higher Hb F level and milder disease phenotype.
Regarding the age of disease presentation, CC genotyped patients had later onset of disease presentation compared to early onset of TT genotype.
The patients were also assessed for organomegaly; cases with CC genotype showed normal or mildly enlarged liver and spleen compared to TT genotype cases who showed moderate and huge organomegaly or splenectomy.
Additionally, CC genotyped patients showed low blood transfusion requirements / year compared to TT genotype that showed higher transfusion requirements. However, genotypes had no relation with serum ferritin levels.
It is recommended to do BCL11A SNP screening on larger number of thalassemia patients and on other hemoglobinopathies to examine the possibility of using it as a prognostic marker for severity of these diseases.