Association between clinical expression and molecular heterogeneity in ß-thalassemia Tunisian patients.
Mol Biol Rep
; 40(11): 6205-12, 2013 Nov.
Article
in En
| MEDLINE
| ID: mdl-24065537
ABSTRACT
Beta-thalassemia is the most frequent hereditary blood disorder in Tunisia because of its geographic localization and history. This pathology is characterized by a complex multisystem process with genetic and biochemical interactions. The aim of this work was to establish phenotype/genotype association through studying the distribution and the relationship between ß-thalassemia and α-thalassemia mutations and three polymorphic markers the C â T polymorphism at -158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)xTy in the ß globin silencer, in two groups of ß-thalassemia major and ß-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to ß(+) -87 (C â G), -30 (T â A) and IVSI-6 (T â C) mutations, haplotypes VIII, IX and Nb and to XmnI polymorphism. The regression analysis of combined genotypes (mutation/XmnI/RFLP haplotype) revealed that they contribute to justify 17.1 % of clinical expression diversity (p < 0.05). Among the studied genotypes the XmnI polymorphism seems to be the most determinant modulating factor, followed by the ß-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of ß-thalassemia that would be responsible of clinical variability.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Thalassemia
/
Genetic Heterogeneity
/
Beta-Globins
/
Genetic Association Studies
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Humans
/
Middle aged
Country/Region as subject:
Africa
Language:
En
Journal:
Mol Biol Rep
Year:
2013
Type:
Article