Association study of common variants with Hb F and Hb A levels in β-thalassaemia carriers of Portuguese ancestry.

Kruppel-like factor 1 (KLF1) is an essential erythroid-specific transcription factor. Several reports have shown that gene mutations are associated with increased levels of Hb F and Hb A. However, scarce population studies have analysed common variations. This study examines the potential association with Hb F and Hb A levels in β-thalassemia (β-thal) carriers of Portugueseancestry of the four common gene variants: -251C>G (rs3817621) and -148G>A (rs79334031), in the promoter region; and c.115A>C (p.Met39Leu) (rs112631212) and c.304T>C (p.Ser102Pro) (rs2072597), in exon 2. Ninety-two Portuguese β-thal carriers (43 males and 49 females) aged 2 to 77 years old (mean 32.55 years) were engaged in the study. Hb F levels range from 0.2 to 12.5% and Hb A was above the normal level, ranging from 3.6 to 6%. The Hb A and Hb F levels were determined by high-performance liquid chromatography. Single-nucleotide polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Minor allele frequencies for SNPs rs3817621 (G), rs79334031 (A), rs112631212 (C) and rs2072597 (C) were 0.196, 0.016, 0.011 and 0.169, respectively. Basic simple linear regression in the total population showed no significant associations with the levels of Hb F (>0.05). For the low-frequency variant -148A, a statistically significant association was found with increased levels of Hb A (β = 0.855; = 0.017). In conclusion, an association signal with Hb A levels was observed for the variant -148A>G (rs79334031). The complex pattern of SNP interactions related to their influence on the transcriptional activity mayexplain the absence of association with Hb F levels.