ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutritional Epidemiology
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1652487
Association of Cord Blood Vitamin D and Genetic Polymorphisms with Childhood Food Allergy in Shanghai, China: A prospective cohort
Provisionally accepted
- 1Department of Developmental and Behavioral Pediatrics, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- 2Developmental and Behavior Pediatrics Department, Fujian Branch of Shanghai Children's Medical Center, Fujian Children's Hospital, Fuzhou, China
- 3Nutrition Department, Wuxi Maternal and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan university, Wuxi, China
- 4MOE-Shanghai Key Lab of Children′s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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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, p=0.779). IL4R rs1801275 AA, IL13 rs20541 GG, and IL-4 rs2243250 CC genotypes synergistically amplified allergy risk under vitamin D deficiency (adjusted OR=26.14, p=0.019; OR=6.51, p=0.025; OR=4.13, p=0.007). Notably, the protective effect of MS4A2 rs569108 GG genotype observed at reference vitamin D levels (adjusted OR=0.55, p=0.016) was attenuated at high levels (OR=0.68, p=0.149). Conclusions: 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.
Keywords: Vitamin D, Genetic polymorphisms, food allergy, Birth cohort, gene-environment interaction
Received: 23 Jun 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Wang, Cai, Pei, Wang, Tian, Zhang and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaodan Yu, Department of Developmental and Behavioral Pediatrics, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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