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

## TL;DR

This study examines genetic variations in the FUT3 gene among Thai blood donors and finds a specific haplotype linked to immune responses against Lewis antigens.

## Contribution

The study is the first to characterize FUT3 variations in Le(a−b−) Thai donors and identifies a haplotype associated with Le antibody responsiveness.

## Key findings

- Thirteen FUT3 SNVs were identified, with c.59T>G present in all Le(a–b–) cases.
- The FUT3*01N.17.03 haplotype showed the strongest association with Le antibody responsiveness.
- No significant differences were found in antibody types or isotypes between groups.

## Abstract

Background: 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. Methods: 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 FUT3 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 FUT3 coding sequence was amplified by polymerase chain reaction and directly sequenced to identify single nucleotide variants (SNVs) and haplotypes. Results: Associations between FUT3 SNVs, haplotypes, and Le antibody responsiveness were subsequently analysed. Thirteen FUT3 SNVs were identified, with c.59T>G (rs28362459) present in all Le(a–b–) cases. The FUT3*01N.17.03 (le59,1067) 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, p < 0.0001). Differences in antibody types, isotypes, and the FUT3*01N.17.03 genotype between groups were not statistically significant. Conclusions: This first study characterises FUT3 variations in Le(a–b–) Thai blood donors and identifies FUT3*01N.17.03 as associated with Le antibody responsiveness, highlighting its relevance for population-specific genetic diagnostics in transfusion medicine.