Genetic Variations of the FUT3 Gene in Le(a−b−) Individuals and Their Association with Lewis Antibody Responses

<b>Background:</b> The biosynthesis of Lewis (Le) antigens depends on the FUT3 gene, encoding an α(1,3/4)-fucosyltransferase. Individuals lacking functional FUT3 exhibit a Le(a-b-) phenotype, regardless of secretor status. <b>Methods:</b> This study determined the prevalence of FUT3 single nucleotide variants (SNVs) in Thai blood donors and characterised genotype and allele distributions. We also examined the association between <i>FUT3</i> variants and the presence of Le antibodies to better understand variability in immune responses. A total of 112 blood donors were recruited, comprising 52 non-responders and 60 responders for Le antibody detection. The <i>FUT3</i> coding sequence was amplified by polymerase chain reaction and directly sequenced to identify single nucleotide variants (SNVs) and haplotypes. <b>Results:</b> Associations between <i>FUT3</i> SNVs, haplotypes, and Le antibody responsiveness were subsequently analysed. Thirteen <i>FUT3</i> SNVs were identified, with c.59T>G (rs28362459) present in all Le(a-b-) cases. The <i>FUT3*01N.17.03</i> (<i>le⁵⁹</i>^,<i>1067</i>) haplotype was most common (0.634) and showed the strongest association with Le antibody responsiveness (adjusted OR = 3.052, 95% CI: 1.683-5.534, <i>p</i> < 0.0001). Differences in antibody types, isotypes, and the <i>FUT3*01N.17.03</i> genotype between groups were not statistically significant. <b>Conclusions:</b> This first study characterises <i>FUT3</i> variations in Le(a-b-) Thai blood donors and identifies <i>FUT3*01N.17.03</i> as associated with Le antibody responsiveness, highlighting its relevance for population-specific genetic diagnostics in transfusion medicine.