Amelioration of Sardinian beta0 thalassemia by genetic modifiers.
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.
Galanello
Renzo
R
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Regionale Microcitemie ASL Cagliari, Cagliari, Italy. renzo.galanello@mcweb.unica.it
Sanna
Serena
S
Perseu
Lucia
L
Sollaino
Maria Carla
MC
Satta
Stefania
S
Lai
Maria Eliana
ME
Barella
Susanna
S
Uda
Manuela
M
Usala
Gianluca
G
Abecasis
Goncalo R
GR
Cao
Antonio
A
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
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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