A large cohort study of genotype and phenotype correlations of beta- Thalassemia in Iranian population

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 β-thalassemia major (tm) or intermedia (ti). multiplex pcr,arms-pcr,rflp-pcr and dna sequencing were performed to identify both α-and β-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 β-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 a-globin gene deletions. the patients inherited concomitant mutations of a- and β-globin,showed no clinical modifications compared with those who had only β-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 β0/β0 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 β-globin genes and ones with just β-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. © 2015,tehran university of medical sciences (tums). all rights reserved.