Relationship of the Interaction Between Two Quantitative Trait Loci with γ-Globin Expression in β-Thalassemia Intermedia Patients

Abstract

Globin switching is a significant factor on blood hemoglobin (Hb) level but its molecular mechanisms have not yet been identified, however, several quantitative trait loci (QTL) and polymorphisms involved regions on chromosomes 2p, 6q, 8q and X account for variation in the γ-globin expression level. We studied the effect of interaction between a region on intron six of the TOX gene, chromosome 8q (chr8q) and XmnI locus on the γ-globin promoter, chr11p on γ-globin expression in 150 β-thalassemia intermedia (β-TI) patients, evaluated by statistical interaction analysis. Our results showed a significant interaction between one QTL on intron six of the TOX gene (rs9693712) and XmnI locus that effect γ-globin expression. Interchromosomal interaction mediates through transcriptional machanisms to preserve true genome architectural features, chromosomes localization and DNA bending. This interaction can be a part of the unknown molecular mechanism of globin switching and regulation of gene expression.

Keywords:

• β-Thalassemia intermedia (β-TI)
• chromosome 8 (chr8q)
• Hb F
• quantitative trait loci (QTL)
• XmnI

Acknowledgments

The authors would like to thank Mr. H. Argasi at the Research Consultation Center (RCC), Shiraz University of Medical Sciences, Shiraz, Iran for his invaluable assistance in editing this article. M. Karimi contributed to the study design, concept, and editing the manuscript; Sh. NickAria wrote the manuscript, study design and laboratory testing; S. Haghapnah contributed to editing the manuscript and statistical analyses; M. Ramzi contributed to editing the manuscript.

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 funded by the Shiraz University of Medical Sciences, Shiraz, Iran [grant no. 150].