The Effect of Five Single Nucleotide Polymorphisms on Hb F Variation of β-Thalassemia Traits and Hematologically Normal Individuals in Southeast Turkey

Abstract

β-Thalassemia (β-thal) is caused by deficiency of β-globin chain synthesis and leads to the accumulation of unstable globin chain production. This results in a higher Hb F level in order to neutralize the excess α chains. In addition, γ-globin gene expression, due to genetic factors after birth, leads to increased Hb F levels in adulthood [hereditary persistence of fetal hemoglobin (Hb) (HPFH)]. In this study, the relationship between β-thal trait and individuals with suspected HPFH and a control group was investigated in Adıyaman, Turkey. Single nucleotide polymorphism (SNP) analyses were performed in five different polymorphic regions using real-time polymerase chain reaction (qPCR) methods [rs4671393 (G>A), rs766432 (A>C), rs9402686 (G>A), rs28384513 (T>G), rs1609812 (A>G)]. No significant difference was found between the control and β-thal group in the codominant inheritance model in the rs1609812 (A>G) polymorphism region only, while all the other polymorphic regions were found to be statistically significant. It was found that different genotype models increased Hb F levels between 1.6- and 3.06-fold in four studied polymorphic regions [rs4671393 (G>A), rs766432 (A>C), rs9402686 (G>A), rs28384513 (T>G)]. All of the polymorphic regions increased the Hb F levels from 1.86- to 24.76-fold, except rs9402686 (G>A) and rs28384513 (T>G) over dominant and rs1609812 (A>G) codominant inheritance models. The AC and AA genotypes increased Hb F levels in the B-cell CLL/lymphoma 11 A haplotype studies. It was determined that both haplotypes 2 and 4 increased Hb F levels. As a result, SNPs strongly affect the Hb F levels in both healthy individuals and β-thal trait.

Keywords:

• β-Thalassemia (β-thal)
• fetal hemoglobin (Hb F)
• haplotype
• polymorphism
• real-time polymerase chain reaction (qPCR)

Acknowledgments

All the authors are employees of Adıyman University, Adıyman, Turkey. They did not receive any scholarship or support from any company or institution other than Adıyaman University, Adıyman, Turkey.

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 by Adıyaman University Research Fund under Grant number SHMYOBAP/2014-0002.