A Large Cohort Study of Genotype and Phenotype Correlations of Beta-Thalassemia in Iranian Population
Maryami، Fereshteh نويسنده Biotechnology Research Center, Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran Maryami, Fereshteh , Azarkeivan، Azita نويسنده Pediatric Hematology Oncology, Transfusion Research center, High Institute for Research and Education in Transfusion Medicine, Department of Thalassemia Clinic, Tehran, Iran Azarkeivan, Azita , Fallah، Mohammad Sadegh نويسنده Gastrointestinal and Liver Diseases Research Center (GLDRC), Gilan University of Medical Sciences, Rasht, Iran. Fallah, Mohammad Sadegh , Zeinali، Sirous نويسنده ,
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 α-globin gene deletions. The patients inherited concomitant mutations of α- 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 patientʹs 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.