A Large Cohort Study of Genotype and Phenotype Correlations of Beta- Thalassemia in Iranian Population.

ABSTRACT

BACKGROUND: Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients. SUBJECTS AND METHODS: In total, 433 patients were clinically classified into ß-thalassemia major (TM) or intermedia (TI). Multiplex PCR, ARMS-PCR, RFLP-PCR and DNA sequencing were performed to identify both α- and ß-globin gene mutations and Xmn1 polymorphism as well. All data were compared and analyzed by SPSS software in TM and TI groups, consequently. RESULTS: A total of 39 different ß-globin mutations were identified. Among them, the most common were IVS IInt1 (40.33%) followed by IVS Int5 (9.56%), C30 (7.22%) and Fr8-9(7%). All patients were subjected to evaluate common α-globin gene deletions. The patients inherited concomitant mutations of α- and ß-globin, showed no clinical modifications compared with those who had only ß-globin mutation. The TI patients showed a significant increase in frequency of both heterozygous and homozygous form of the Xmn1 polymorphism. It was also found that ß(0)/ß(0) genotype patients, inherited the Xmn1 polymorphism required lesser blood transfusion. CONCLUSION: No significant differences were observed, on the severity of disease, between patient's inherited defective α- and ß-globin genes and ones with just ß-globin gene mutation. Taking the results of this research into account, Xmn1 polymorphism can be considered as an important genetic factor modulating the severity of disease.