ArticlePediatric research2026
Profile of human milk oligosaccharides and maternal FUT2 polymorphism: genotype-phenotype correlation and proposed cut-off for secretor status.
Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHuman milk oligosaccharides (HMO) are complex carbohydrates which is undigestible to humans and confer health benefits. The synthesis of HMOs is determined by fucosyltransferase enzymes, which are encoded by FUT2/FUT3 genes. Polymorphisms of the FUT2 result in various secretor status. This study aimed to identify the proportion of secretor and FUT2 genotype-phenotype correlation in Indonesian mothers.
methodsThis was a cross-sectional study, recruiting 120 healthy mothers aged at least 18 years who exclusively breastfed. Breastmilk samples were obtained at infant's age 2-5 weeks old. Analysis of HMO was performed using Ultra High-Performance Liquid Chromatography-Fluorescence Detection. Sequencing of entire coding region was performed to find genetic variants of FUT2. The ROC analysis was done to determine the threshold value of 2'FL based on FUT2 genotype.
resultsThe proportion of secretor was 65.8%. A novel FUT2 variant was identified, c.851C>G. There was a significant association between secretor genotype and phenotype (p < 0.001). A threshold value of 425.9 mg/L for 2'FL was obtained, with 98.7% sensitivity and 100% specificity.
conclusionProportion of secretor in Indonesian is lower than of Caucasian. The widely used 2'FL cut-off at 25-50 mg/L needs to be re-evaluated based on clinical health impact or genotype findings. IMPACT: This study answered the question of secretor proportion in Indonesian mothers (65.8%). The significant differences among countries implied that the consequences of secretor status to infant's health should be elaborated, including the contribution of less common HMOs. We demonstrated a strong correlation between FUT2 genotype-phenotype and discovered a novel FUT2 variant, c.851C>G. This study obtained a secretor cut-off at 2'FL 425 mg/L based on ROC curve for FUT2 genotype and 2'FL values. This cut-off needs to be evaluated in light of clinical impact, ideally in a longitudinal study design to capture dynamic of human milk across lactation period.
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