Inverse Association of Galactosyl Transferase A c.991G > A (p.G331S) Gene Polymorphism with Anti-A1 Production in A2...

The A2 phenotype, a subgroup of blood group A, accounts for 10% of blood group A cases, while A2B represents 1%. A1 cells express more carbohydrate precursors than A2, which mainly displays types 1 and 2. Anti-A1 antibodies, present in some A2 (1-8%) and A2B (22-35%) cases, can complicate transfusions. This study examines the relationship between single nucleotide variants (SNVs) in the galactosyltransferase A (GTA) gene and anti-A1 antibody production in A2 and A2B blood groups. Conducted at the Vesal Blood Transfusion Center, Tehran (October 2023 - June 2024), the study involved male donors with A2 or A2B phenotypes. Donors with anti-A1 antibodies formed the case group, while those without formed the control group. Exon 7 of the GTA gene from 25 samples per group was sequenced to identify SNVs. Among 1,489 samples, 27 (5.6%) were A2 and 90 (31.6%) were A2B. Anti-A1 antibodies were found in 44.4% of A2 and 54.4% of A2B individuals. The GTA G991A (p.G331S) polymorphism showed a significant inverse association with anti-A1 presence (OR = 0.34, P = 0.047). The coinheritance of several SNVs was linked to anti-A1 titers but lacked statistical significance. The study suggests a higher prevalence of anti-A1 in A2 and A2B individuals than previously reported and highlights the GTA G991A polymorphism's role in anti-A1 production. Further research is needed to explore these genetic mechanisms.