Analysis of β globin gene mutations and Gγ XmnI polymorphism in thalassemia intermedia patients referred to Ali-Asghar Hospital, Tehran

Background and Objectives The molecular basis for thalassemia intermedia (TI) is determined in most thalasemia affected countries, but in Iran there has been no perfect investigation so far. This report is the results of the first step of a comprehensive analysis on molecular basis of TI in Iran. Two most important factors influencing the phenotype of TI, i.e. beta globin gene mutations, Gγ XmnI polymorphism, and genotype/phenotype correlation in these patients were analysed. Materials and Methods In an experimental pilot study, 42 TI patients who referred to Ali-Asghar Hospital were selected and genomic DNA was extracted by salting out method. The ARMS-PCR technique was performed to detect the most prevalent β thalassemia mutations in Iran: IVSII-1 (G>A). Direct DNA sequencing was performed on the samples which had at least one unidentified allele. Simultaneously, Gγ XmnI polymorphism was determined using PCR-RFLP procedure. Afterwards, the association of this polymorphism with TI was analyzed. Results Among 76 chromosomes, IVSII-1 was the most frequent mutation detected with 42 alleles (55.26%). Totally, 66 β globin alleles (86.84%) were β0 and 7 (9.21%) β+. In addition, 61 chromosomes (80.26%) were positive for XmnI polymorphism. This polymorphism was in strong linkage to β0 mutations, mainly IVSII-1. No cases with IVSII-1 mutation were XmnI-/-. Conclusions It seems that the presence of XmnI polymorphism may play an important role in reducing the clinical severity of thalassemia in patients with severe β0 alleles. However, other genetic factors should be also investigated.