Association Between Genetic Polymorphisms and Hb F Levels in Heterozygous β-Thalassemia 3.5 kb Deletions.

Single nucleotide polymorphisms (SNPs) in several genetic modifying factors have been related to Hb F levels, including Gγ XmnI polymorphism, B-cell lymphoma/leukemia 11 A (BCL11A), HBS1L-MYB intergenic polymorphism (HMIP) and a mutation in the Krüppel-like factor 1 (KLF1). This study aimed to determine whether genetic variability of these modifying factors affects Hb F levels in heterozygous β-thalassemia (β-thal) 3.5 kb deletion (NC_000011.10: g.5224302-5227791del13490bp). A total of 111 β-thal 3.5 kb deletion carriers with Hb F levels ranging from 0.9 to 18.4% was recruited for this study. Genotyping of SNPs including HBG2 rs7482144, HMIP rs4895441 and rs9399137, BCL11A rs4671393 and KLF1 rs2072596 was identified. Multiple regression analyses showed that only two SNPs (HMIP rs4895441 and rs9399137) influenced Hb F levels. Interestingly, a combination of these two SNPs was associated with higher Hb F levels. Our study is the first to demonstrate that the rs4895441, rs9399137 of HMIP are associated with elevated Hb F levels in the heterozygous β-thal 3.5 kb deletion.