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

Abstract

β-Thalassemia intermedia (β-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 β-TI in Iran. To elucidate the mild phenotype of many patients with β-TI, we screened for three prevalent β-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 α-globin genes, XmnI polymorphisms and restriction fragment length polymorphism (RFLP) haplotypes on the β-globin gene cluster in 50 β-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 β-TI patients. The XmnI polymorphism is defined in association with this prevalent mutation. Two patients had a single α-globin gene deletion [–α^3.7 (rightward) deletion]. The main genetic factor in mild phenotype β-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 β-TI, especially with the homozygous HBB: c.315+1G>A mutation. Molecular basis of β-TI could be explained by the involvement of different factors that tend to develop the disease phenotype.

Keywords:

• β-Thalassemia intermedia (β-TI)
• haplotype
• HBB: c.315+1G>A
• HBB: c.92+5G>C
• HBB: c.93-21G>A
• Xmnl polymorphism

Acknowledgments

This study was completed at the Genetics Laboratory of the University of Isfahan, Isfahan, Iran. We wish to extend our sincere gratitude to all physicians and nurses at the Omid Hospital (Isfahan, Iran), who all contributed to this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported financially by the Departments of Research/Technology and Graduate Office (Isfahan University, Isfahan, Iran).