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.