| Summary: | Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at <i>BCL11A</i>, <i>HBS1L-MYB</i> and <i>HBB</i> with HbF levels in 237 Kuwaiti SCD patients, divided into 3 subgroups according to their HbF levels. Illumina Ampliseq custom DNA panel was used for genotyping and confirmed by arrayed primer extension or Sanger sequencing. In the <i>BCL11A</i> locus, the CC genotype of rs7606173 [χ<sup>2</sup> = 16.5] and (GG) of rs10195871 [χ<sup>2</sup> = 15.0] were associated with Hb-F1 and HbF-2 subgroups, unlike rs1427404-T [χ<sup>2</sup> = 17.3], which showed the highest association across the three subgroups. <i>HBS1L-MYB</i> locus revealed 2 previously-described SNPs (rs66650371 [<i>χ</i><sup>2</sup> = 9.5] and rs35795442 [χ<sup>2</sup> = 9.2]) and 2 previously-unreported SNPs, (rs13220662 [χ<sup>2</sup> = 6.2] and rs1406811 [χ<sup>2</sup> = 6.7]) that were associated with the HbF-3 subgroup, making this the key locus elevating HbF to the highest levels. <i>HBB</i> cluster variants were associated with lower levels of HbF (β = −1.1). We report four previously-unpublished variants showing significant association with HbF. Each of the three quantitative trait loci affects HbF levels differently; unique SNPs, especially in <i>HBS1L-MYB</i>, elevate HbF to the highest levels.
|
|---|
