Association between Different Polymorphic Markers and β-Thalassemia Intermedia in Central Iran.

beta-Thalassemia intermedia (beta-TI) is a clinical condition characterized by moderate, non transfusional anemia and hepatosplenomegaly. The main objective of this study was to determine the molecular basis of the clinical phenotype of beta-TI in Iran. To elucidate the mild phenotype of many patients with beta-TI, we screened for three prevalent beta-globin gene mutations [IVS-II-1 (G>A) HBB: c.315+1G>A, IVS-I-110 (G>A) HBB: c.93-21G>A and IVS-I-5 (G>C) [HBB: c.92+5G>C], deletions on the alpha-globin genes, XmnI polymorphisms and restriction fragment length polymorphism (RFLP) haplotypes on the beta-globin gene cluster in 50 beta-TI patients. Fifty-eight percent of the patients (29 cases) were associated with the mentioned mutations. We showed that the HBB: c.315+1G>A mutation is linked to haplotype [+ - + +] (57.69%). This haplotype is in linkage disequilibrium with the XmnI polymorphism (NG_000007.3: g.42677C>T) and has been associated with increased expression of Hb F in beta-TI patients. The XmnI polymorphism is defined in association with this prevalent mutation. Two patients had a single alpha-globin gene deletion [-alpha(3.7) (rightward) deletion]. The main genetic factor in mild phenotype beta-TI patients is the linkage of an XmnI polymorphism (NG_000007.3: g.42677C>T) with the HBB: c.315+1G>A (80.76%), which is associated with increased production of Hb F and coinheritance of haplotype [+ - + +] with beta-TI, especially with the homozygous HBB: c.315+1G>A mutation. Molecular basis of beta-TI could be explained by the involvement of different factors that tend to develop the disease phenotype.