Regulatory Single Nucleotide Polymorphism rs368698783 (G>A): a Genetic Modifier of Hb F Production Only under Erythropoietic Stress Characteristic for β-Globin Chain Deficiency?

Abstract

A regulatory single nucleotide polymorphism (rSNP), the ^Aγ (+25 G>A) (rs368698783) (NG_000007.3: g47783G>A) located in the HBG1 proximal promoter, is a significant predictor of clinical severity by elevating Hb F levels in β-thalassemia (β-thal). In this study, the presence of the ^Aγ (+25 G>A) and ^Aγ (+25 A>A) genotypes was investigated in four subgroups from a total of 611 subjects, including 88 α-thalassemia (α-thal) carriers (group A), 162 β-thal carriers of point mutations (group B), 57 carriers of β-thal deletions (group C) and 152 non thalassemic individuals (group D). The result is that the genotypes G>A and A>A exhibit significantly high levels of Hb F compared with the genotype G>G in both groups B and C, while no significant difference was observed in both groups A and D. We assume that the effect of ^Aγ (+25 G>A) polymorphism on Hb F production is only under erythropoietic stress characteristic for β-globin chain deficiency.

Keywords:

• β-Thalassemia (β-thal)
• regulatory single nucleotide polymorphism (rSNP) rs368698783
• fetal hemoglobin (Hb)
• erythropoietic stress

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by Health and Family Planning Commission of Guangdong Province [2016119153114316].