title: 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.affiliation: Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Regionale Microcitemie ASL Cagliari, Cagliari, Italy. renzo.galanello@mcweb.unica.it
authors.forename: Renzo
authors.initials: R
authors.lastname: Galanello
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Lucia
authors.initials: L
authors.lastname: Perseu
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Sollaino
authors.forename: Stefania
authors.initials: S
authors.lastname: Satta
authors.forename: Maria Eliana
authors.initials: ME
authors.lastname: Lai
authors.forename: Susanna
authors.initials: S
authors.lastname: Barella
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Gianluca
authors.initials: G
authors.lastname: Usala
authors.forename: Goncalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000378:metabolism; D040641:Quantitative Trait Loci / Q000235:genetics; D012097:Repressor Proteins; D017085:alpha-Thalassemia / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D005319:Fetal Hemoglobin
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