Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort
BackgroundEmerging 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 interac...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1652487/full |
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| author | Xirui Wang Yingying Cai Jingjing Pei Bin Wang Ying Tian Jun Zhang Xiaodan Yu Xiaodan Yu |
| author_facet | Xirui Wang Yingying Cai Jingjing Pei Bin Wang Ying Tian Jun Zhang Xiaodan Yu Xiaodan Yu |
| author_sort | Xirui Wang |
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| description | BackgroundEmerging 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.MethodsA 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.ResultsA 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).ConclusionGenetic 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. |
| format | Article |
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| institution | Kabale University |
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| spelling | doaj-art-585ecee1e5834224a1f39db315e13f632025-08-25T04:10:20ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-08-011210.3389/fnut.2025.16524871652487Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohortXirui Wang0Yingying Cai1Jingjing Pei2Bin Wang3Ying Tian4Jun Zhang5Xiaodan Yu6Xiaodan Yu7Department of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Pudong, Shanghai, ChinaDevelopmental and Behavior Pediatrics Department, Fujian Branch of Shanghai Children’s Medical Center, Fujian Children’s Hospital, Fuzhou, ChinaNutrition Department, Wuxi Maternal and Child Health Care Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, ChinaDepartment of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Pudong, Shanghai, ChinaMOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Yangpu, Shanghai, ChinaMOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Yangpu, Shanghai, ChinaDepartment of Developmental and Behavioral Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Pudong, Shanghai, ChinaMOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Yangpu, Shanghai, ChinaBackgroundEmerging 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.MethodsA 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.ResultsA 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).ConclusionGenetic 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.https://www.frontiersin.org/articles/10.3389/fnut.2025.1652487/fullvitamin Dgenetic polymorphismsfood allergybirth cohortgene–environment interaction |
| spellingShingle | Xirui Wang Yingying Cai Jingjing Pei Bin Wang Ying Tian Jun Zhang Xiaodan Yu Xiaodan Yu Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort Frontiers in Nutrition vitamin D genetic polymorphisms food allergy birth cohort gene–environment interaction |
| title | Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort |
| title_full | Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort |
| title_fullStr | Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort |
| title_full_unstemmed | Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort |
| title_short | Association of cord blood vitamin D and genetic polymorphisms with childhood food allergy in Shanghai, China: a prospective cohort |
| title_sort | association of cord blood vitamin d and genetic polymorphisms with childhood food allergy in shanghai china a prospective cohort |
| topic | vitamin D genetic polymorphisms food allergy birth cohort gene–environment interaction |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1652487/full |
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