Association between clinical expression and molecular heterogeneity in β-thalassemia Tunisian patients.
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 β-thalassemia and α-thalassemia mutations and three polymorphic markers: the C → T polymorphism at -158 of the Gγ gene, the RFLP haplotype and the repeated sequence (AT)xTy in the β globin silencer, in two groups of β-thalassemia major and β-thalassemia intermedia (TI) patients. Statistical analysis has shown that moderate expression seen in TI patients was significantly associated to β(+) -87 (C → G), -30 (T → A) and IVSI-6 (T → 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 β-thalassemia mutation and RFLP haplotype. Our findings highlight the heterogeneity of molecular background of β-thalassemia that would be responsible of clinical variability.
Biochemistry Laboratory (Research Laboratory "Haemoglobinopathies and Cystic Fibrosis), Children's Hospital, Lab Santé 01", Bab Saadoun Square, 1007, Tunis, Tunisia, latifa.b.jouini@gmail.com.
L
L
Jouini
C A
CA
Sahli
N
N
Laaouini
F
F
Ouali
I
I
Ben Youssef
B
B
Dakhlaoui
R
R
Othmeni
F
F
Ouennich
S
S
Hadj Fredj
H
H
Siala
M
M
Becher
N E
NE
Toumi
S
S
Fattoum
R
R
Hafsia
A
A
Bibi
T
T
Messaoud
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D023061:Gene Order; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D059372:Nucleotide Motifs; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D014416:Tunisia; D055815:Young Adult; D017085:alpha-Thalassemia / Q000235:genetics / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics
D006454:Hemoglobins; D055544:beta-Globins; D055545:gamma-Globins