title: Molecular analysis of gamma-globin promoters, HS-111 and 3'HS1, in beta-thalassemia intermedia patients associated with high levels of Hb F.
abstract: The nucleotide (nt) variations in the promoter region of the gamma-globin genes, HS-111 and 3'HS1 regions, were studied in Iranian patients with beta-thalassemia intermedia (beta-TI), beta-thalassemia major (beta-TM) and healthy individuals. Of the five nt variations at the 5' end of the (A)gamma-globin gene, -369 (C>G), -611 (-T) and -603/604 (GA>AG) were found in all samples, whereas -588 (A>G) and -AAGC at -222 to -225 were found at different frequencies in the studied groups. Therefore, the -369, -611 and -603/604 variations were considered common mutations in this population, and the difference with respect to the -AAGC deletion was not significant. However, the A allele of the -588 variation and [+] allele of the XmnI polymorphism were more frequent in beta-TI patients, especially those who had the IVS-II-1(G>A)/IVS-II-1(G>A) genotype. The + allele of XmnI also had complete correlation with the A allele of -588 variation. The HS-111 (-21 A) variation also showed association with beta-TI patients who had high levels of Hb F. Bearing in mind that the -588 variation lies within the postulated adult-specific silencer region and that the majority of beta-TI patients had allele A, then it can be envisaged that this allele could have a role in altering the repressor function at this region. Therefore, the A allele of -588, [+] allele of XmnI and HS-111 (-21 A) variation are useful genetic markers to differentiate between beta-TM and beta-TI patients. However, these nt changes alone may not be the only elements raising the level of Hb F, other regulatory and modifying factors also play a role in Hb F production.
authors: Department of Clinical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors: Mohammad
authors: M
authors: Hamid
authors: Frouzandeh
authors: F
authors: Mahjoubi
authors: Mohammad T
authors: MT
authors: Akbari
authors: Aida
authors: A
authors: Arab
authors: Sirous
authors: S
authors: Zeinali
authors: Morteza
authors: M
authors: Karimipoor
mesh_terms: D016022:Case-Control Studies; D005319:Fetal Hemoglobin / Q000032:analysis*; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D007492:Iran; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D055545:gamma-Globins; D005319:Fetal Hemoglobin