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

Abstract

beta-Thalassemia (beta-thal) is caused by deficiency of beta-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 alpha chains. In addition, gamma-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 beta-thal trait and individuals with suspected HPFH and a control group was investigated in Adiyaman, 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 beta-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 beta-thal trait.