Variation in Hemoglobin F Production Among Normal and Sickle Cell Adults Is Not Related to Nucleotide Substitutions in the Gamma Promoter Regions

• Published in: Blood 1991-01, Vol.77 (1), p.174-177
• Main Authors: Economou, E.P., Antonarakis, S.E., Kazazian, H.H., Serjeant, G.R., Dover, G.J.
• Format: Article
• Language: English
• Subjects: Adult; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - genetics; Anemias. Hemoglobinopathies; Base Sequence; Biological and medical sciences; Diseases of red blood cells; DNA - blood; DNA - genetics; DNA - isolation & purification; Fetal Hemoglobin - genetics; Genetic Variation; Globins - genetics; Haplotypes; Hematologic and hematopoietic diseases; Humans; Medical sciences; Molecular Sequence Data; Oligonucleotide Probes; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Reference Values
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V77.1.174.174

Single nucleotide substitutions in the promoter regions of the Ay- and Gγ-globin genes have been associated with increased fetal hemoglobin (HbF) production. We wished to determine whether these or other unrecognized substitutions in the γ promoter regions are responsible for the 20-fold variation in HbF production in sickle cell patients or normal adults. From a random sampling of 250 sickle cell (SS) patients and 125 normal adults, 17 individuals representing the highest and lowest HbF producers were selected for study. All three common restriction fragment length polymorphism β-globin region haplotypes (Benin, Central African Republic, and Senegal) were found in both the highest and lowest HbF producers with SS disease. Using the polymerase chain reaction amplification and direct sequencing of the amplified DNA product, we examined the promoter regions of both the Aγ and Gγ genes from -350 bp to +50 bp of the CAP site. No mutations were found in either γ gene promoter region. We conclude that nucleotide substitutions in the promoter regions (-350 to +50 bp) of bothγ genes are not responsible for the marked variation in HbF production among SS or normal individuals.