A genetic score for the prediction of beta-thalassemia severity.
Haematologica
; 100(4): 452-7, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25480500
ABSTRACT
Clinical and hematologic characteristics of beta(ß)-thalassemia are determined by several factors resulting in a wide spectrum of severity. Phenotype modulators are HBB mutations, HBA defects and fetal hemoglobin production modulators (HBG2g.-158C>T polymorphism, HBS1L-MYB intergenic region and the BCL11A). We characterized 54 genetic variants at these five loci robustly associated with the amelioration of beta-thalassemia phenotype, to build a predictive score of severity using a representative cohort of 890 ß-thalassemic patients. Using Cox proportional hazard analysis on a training set, we assessed the effect of these loci on the age at which patient started regular transfusions, built a Thalassemia Severity Score, and validated it on a testing set. Discriminatory power of the model was high (C-index=0.705; R(2)=0.343) and the validation conducted on the testing set confirmed its predictive accuracy with transfusion-free survival probability (P<0.001) and with transfusion dependency status (Area Under the Receiver Operating Characteristic Curve=0.774; P<0.001). Finally, an automatized on-line calculation of the score was made available at http//tss.unica.it. Besides the accurate assessment of genetic predictors effect, the present results could be helpful in the management of patients, both as a predictive score for screening and a standardized scale of severity to overcome the major-intermedia dichotomy and support clinical decisions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Talassemia beta
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Globinas beta
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article