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An Aγ-globin G->A gene polymorphism associated with β 0 39 thalassemia globin gene and high fetal hemoglobin production.
- Source :
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BMC medical genetics [BMC Med Genet] 2017 Aug 29; Vol. 18 (1), pp. 93. Date of Electronic Publication: 2017 Aug 29. - Publication Year :
- 2017
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Abstract
- Background: Increase of the expression of γ-globin gene and high production of fetal hemoglobin (HbF) in β-thalassemia patients is widely accepted as associated with a milder or even asymptomatic disease. The search for HbF-associated polymorphisms (such as the XmnI, BCL11A and MYB polymorphisms) has recently gained great attention, in order to stratify β-thalassemia patients with respect to expectancy of the first transfusion, need for annual intake of blood, response to HbF inducers (the most studied of which is hydroxyurea).<br />Methods: Aγ-globin gene sequencing was performed on genomic DNA isolated from a total of 75 β-thalassemia patients, including 31 β <superscript>0</superscript> 39/β <superscript>0</superscript> 39, 33 β <superscript>0</superscript> 39/β <superscript>+</superscript> IVSI-110, 9 β <superscript>+</superscript> IVSI-110/β <superscript>+</superscript> IVSI-110, one β <superscript>0</superscript> IVSI-1/β <superscript>+</superscript> IVSI-6 and one β <superscript>0</superscript> 39/β <superscript>+</superscript> IVSI-6.<br />Results: The results show that the rs368698783 polymorphism is present in β-thalassemia patients in the 5'UTR sequence (+25) of the Aγ-globin gene, known to affect the LYAR (human homologue of mouse Ly-1 antibody reactive clone) binding site 5'-GGTTAT-3'. This Aγ(+25 G->A) polymorphism is associated with the Gγ-globin-XmnI polymorphism and both are linked with the β <superscript>0</superscript> 39-globin gene, but not with the β <superscript>+</superscript> IVSI-110-globin gene. In agreement with the expectation that this mutation alters the LYAR binding activity, we found that the Aγ(+25 G->A) and Gγ-globin-XmnI polymorphisms are associated with high HbF in erythroid precursor cells isolated from β <superscript>0</superscript> 39/β <superscript>0</superscript> 39 thalassemia patients.<br />Conclusions: As a potential explanation of our findings, we hypothesize that in β-thalassemia the Gγ-globin-XmnI/Aγ-globin-(G->A) genotype is frequently under genetic linkage with β <superscript>0</superscript> -thalassemia mutations, but not with the β <superscript>+</superscript> -thalassemia mutation here studied (i.e. β <superscript>+</superscript> IVSI-110) and that this genetic combination has been selected within the population of β <superscript>0</superscript> -thalassemia patients, due to functional association with high HbF. Here we describe the characterization of the rs368698783 (+25 G->A) polymorphism of the Aγ-globin gene associated in β <superscript>0</superscript> 39 thalassemia patients with high HbF in erythroid precursor cells.
Details
- Language :
- English
- ISSN :
- 1471-2350
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 28851297
- Full Text :
- https://doi.org/10.1186/s12881-017-0450-3