Amelioration of Sardinian beta0 thalassemia by genetic modifiers.

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.
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)
Chemical References	BCL11A protein, human Carrier Proteins Nuclear Proteins Proto-Oncogene Proteins c-myb Repressor Proteins Fetal Hemoglobin
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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