Molecular basis of weak A subgroups in the Korean population: Identification of three novel subgroup-causing variants in the ABO regulatory regions

Background Recent studies on Chinese and Japanese populations have shown that weak ABO subgroups could be caused by variants in the major regulatory regions of ABO, the proximal promoter, +5.8-kb site, and CCAAT-binding factor/NF-Y binding site. We investigated the molecular basis of weak A subgroups in the Korean population. Study design and methods This study included 11 samples suspected to have a weak A subgroup. These samples were subjected to sequencing analysis of ABO exons 6 and 7. If no subgroup-causing variants were detected in this region, exons 1-5 and three major regulatory regions were sequenced. Results Sequencing analysis of exons 6 and 7 detected two known subgroup alleles (ABO*AW.10, n = 5; ABO*AEL.02, n = 2). The remaining four samples contained a sequence variant in the proximal promoter (g.4944C>T, n = 1; g.4954G>T, n = 1) or +5.8-kb site (g.10843T>C, n = 1; g.10935C>T, n = 1). Notably, three of the four variants (g.4944C>T, g.4954G>T, and g.10843T>C) have not been reported previously in weak ABO subgroups. Conclusion This study provides the first evidence that alterations in the proximal promoter and + 5.8-kb site could account for a substantial proportion of weak A subgroups in the Korean population.