Dataset Information

Role of XmnIgG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate ?-Thalassemia Patients.

ABSTRACT: BACKGROUND:?-thalassemia is the most common monogenic disorder in human. The (C-->T) polymorphism at -158 upstream region of the ?G-globin gene and pharmacological factors such as hydroxyurea have been reported to influence ?-globin gene expression and the severity of clinical symptoms of ?-thalassemia. METHODS:In the present study, 51 ?-thalassemia intermediate patients were studied. Xmn1?G polymorphism genotype was determined using Tetra-Primer ARMS-PCR technique. Hemoglobin (Hb) and fetal hemoglobin (HbF) levels were determined by gel electrophoresis. RESULTS:Of 51 patients, 35 (68.6%) patients were heterozygous (CT) and 16 (31.4%) patients were homozygous (CC). Of 30 patients under treatment by hydroxyurea, 20 (66.7%) patients were heterozygous (CT) and 10 (33.3%) patients were homozygous (CC). Our results demonstrated that in the heterozygous (CT) genotype, the Hb (9.58 ± 1.25 gm/dl) and HbF (89.30 ± 21.87) levels were significantly higher in comparison with homozygous (CC) genotype (7.94 ± 1.34 gm/dl and 70.32 ± 40.56, respectively). Furthermore, we observed that after drug usage, the Hb and HbF levels in patients with heterozygous (CT) genotype (0.7 ± 1.26 gm/dl and 5.95 ± 14.8, respectively) raised more in comparison with homozygous (CC) genotype (0.26 ± 1.43 gm/dl and 0.8 ± 1.31, respectively). CONCLUSION:Hb and HbF levels in the patients carrying T allele are increased significantly, and they also response to hydroxyurea treatment.

SUBMITTER: Motovali-Bashi M

PROVIDER: S-EPMC4571014 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of XmnIgG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate β-Thalassemia Patients.

Motovali-Bashi Majid M Ghasemi Tayyebeh T

Iranian biomedical journal 20150530 3

<h4>Background</h4>β-thalassemia is the most common monogenic disorder in human. The (C-->T) polymorphism at -158 upstream region of the γG-globin gene and pharmacological factors such as hydroxyurea have been reported to influence γ-globin gene expression and the severity of clinical symptoms of β-thalassemia.<h4>Methods</h4>In the present study, 51 β-thalassemia intermediate patients were studied. Xmn1γG polymorphism genotype was determined using Tetra-Primer ARMS-PCR technique. Hemoglobin (Hb ...[more]

PMID: 26024726

Similar Datasets

Project description: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.

Dataset Information

Role of XmnIgG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate ?-Thalassemia Patients.

Publications

Role of XmnIgG Polymorphism in Hydroxyurea Treatment and Fetal Hemoglobin Level at Isfahanian Intermediate β-Thalassemia Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets