GENETIC FACTORS INFLUENCING HEMOGLOBIN F LEVEL IN beta-THALASSEMIA/HB E DISEASE

Genetic factors influencing Hb F content in adult red blood cells include beta-thalassemia genotypes, co-inheritance of alpha-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of alpha- and beta-thalassemia and five SNPs in beta-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in beta-thalassemia were performed in 81 subjects diagnosed with beta-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild beta-thalassemia (0.8-2.5 g/dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with alpha-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of beta-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of gamma-globin genes leads to amelioration of beta-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future.