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An A?-globin G->A gene polymorphism associated with ?039 thalassemia globin gene and high fetal hemoglobin production.

ABSTRACT: Increase of the expression of ?-globin gene and high production of fetal hemoglobin (HbF) in ?-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 ?-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).A?-globin gene sequencing was performed on genomic DNA isolated from a total of 75 ?-thalassemia patients, including 31 ?039/?039, 33 ?039/?+IVSI-110, 9 ?+IVSI-110/?+IVSI-110, one ?0IVSI-1/?+IVSI-6 and one ?039/?+IVSI-6.The results show that the rs368698783 polymorphism is present in ?-thalassemia patients in the 5'UTR sequence (+25) of the A?-globin gene, known to affect the LYAR (human homologue of mouse Ly-1 antibody reactive clone) binding site 5'-GGTTAT-3'. This A?(+25 G->A) polymorphism is associated with the G?-globin-XmnI polymorphism and both are linked with the ?039-globin gene, but not with the ?+IVSI-110-globin gene. In agreement with the expectation that this mutation alters the LYAR binding activity, we found that the A?(+25 G->A) and G?-globin-XmnI polymorphisms are associated with high HbF in erythroid precursor cells isolated from ?039/?039 thalassemia patients.As a potential explanation of our findings, we hypothesize that in ?-thalassemia the G?-globin-XmnI/A?-globin-(G->A) genotype is frequently under genetic linkage with ?0-thalassemia mutations, but not with the ?+-thalassemia mutation here studied (i.e. ?+IVSI-110) and that this genetic combination has been selected within the population of ?0-thalassemia patients, due to functional association with high HbF. Here we describe the characterization of the rs368698783 (+25 G->A) polymorphism of the A?-globin gene associated in ?039 thalassemia patients with high HbF in erythroid precursor cells.

SUBMITTER: Breveglieri G 

PROVIDER: S-EPMC5575872 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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An Aγ-globin G->A gene polymorphism associated with β<sup>0</sup>39 thalassemia globin gene and high fetal hemoglobin production.

Breveglieri Giulia G   Bianchi Nicoletta N   Cosenza Lucia Carmela LC   Gamberini Maria Rita MR   Chiavilli Francesco F   Zuccato Cristina C   Montagner Giulia G   Borgatti Monica M   Lampronti Ilaria I   Finotti Alessia A   Gambari Roberto R  

BMC medical genetics 20170829 1

<h4>Background</h4>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 (th  ...[more]

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