Abstract |
Sardinian beta-thalassemia patients all are homozygotes for the same null allele in the beta-globin gene, but the clinical manifestations are extremely variable in severity. Previous studies have shown that the coinheritance of alpha-thalassemia or the presence of genetic variants that sustain fetal hemoglobin production has a strong impact on ameliorating the clinical phenotype. Here we evaluate the contribution of variants in the BCL11A, and HBS1L-MYB genes, implicated in the regulation of fetal hemoglobin, and of alpha-thalassemia coinheritance in 50 thalassemia intermedia and 75 thalassemia major patients. We confirm that alpha-thalassemia and allele C of single nucleotide polymorphism rs-11886868 in BCL11A were selectively represented in thalassemia intermedia patients. Moreover, allele G at single nucleotide polymorphism rs9389268 in the HBS1L-MYB locus was significantly more frequent in the thalassemia intermedia patients. This trio of genetic factors can account for 75% of the variation differences in phenotype severity.
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Authors | Renzo Galanello, Serena Sanna, Lucia Perseu, Maria Carla Sollaino, Stefania Satta, Maria Eliana Lai, Susanna Barella, Manuela Uda, Gianluca Usala, Goncalo R Abecasis, Antonio Cao |
Journal | Blood
(Blood)
Vol. 114
Issue 18
Pg. 3935-7
(Oct 29 2009)
ISSN: 1528-0020 [Electronic] United States |
PMID | 19696200
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- BCL11A protein, human
- Carrier Proteins
- Nuclear Proteins
- Proto-Oncogene Proteins c-myb
- Repressor Proteins
- Fetal Hemoglobin
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Topics |
- Adolescent
- Adult
- Alleles
- Carrier Proteins
(genetics, metabolism)
- Female
- Fetal Hemoglobin
(biosynthesis, genetics)
- Homozygote
- Humans
- Italy
- Male
- Middle Aged
- Nuclear Proteins
(genetics, metabolism)
- Polymorphism, Single Nucleotide
- Proto-Oncogene Proteins c-myb
(genetics, metabolism)
- Quantitative Trait Loci
(genetics)
- Repressor Proteins
- alpha-Thalassemia
(genetics, metabolism)
- beta-Thalassemia
(genetics, metabolism)
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