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.

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