ArticleFrontiers in nutrition2025
Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort.
Article in Frontiers in nutrition, 2025. 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
Background: Emerging evidence suggests vitamin D plays a dual role in immune regulation, yet its interplay with genetic susceptibility in early-life allergy development remains poorly understood. This prospective cohort study investigated whether cord blood 25-hydroxyvitamin D [25(OH)D] levels interact with immunoregulatory gene variants to influence childhood food allergy risk. Methods: A total of 1,049 mother-infant pairs from the Shanghai Allergy Cohort were stratified by cord blood 25(OH)D concentrations (<15, 15-25, >25 ng/mL). Food allergy diagnoses at 6, 12, and 24 months followed standardized clinical criteria. Five single-nucleotide polymorphisms (SNPs) (IL4, IL4R, IL13, MS4A2) were genotyped using MALDI-TOF MS. Multivariable logistic regression evaluated associations between vitamin D, genetic polymorphisms, and allergy outcomes, adjusting for birth season, maternal allergy history, and environmental confounders. Gene-vitamin D interactions were tested via stratified analyses. Results: A U-shaped relationship was observed between cord blood serum25(OH)D levels and the risk of developing childhood food allergies. Both deficient (<15 ng/mL) and elevated (>25 ng/mL) 25(OH)D levels at birth independently increased 6-month food allergy risk (adjusted OR = 2.55 and 2.38, respectively). By 24 months, only deficient levels showed attenuated effects (OR = 1.14, Conclusion: Genetic susceptibility in Th2 pathway genes (IL4R, IL-4, IL13) dramatically amplified food allergy risk under vitamin D deficiency, with AA/GG/CC genotypes conferring 4- to 26-fold increased susceptibility. Conversely, the protective effect of MS4A2 rs569108 GG genotype was compromised at high vitamin D levels (>25 ng/mL). Our findings underscore that personalized vitamin D thresholds during pregnancy must account for fetal genetic background to mitigate allergy risk.
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