Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital, Children's Memorial Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Allergy. 2011 Nov;66(11):1442-8. doi: 10.1111/j.1398-9995.2011.02681.x. Epub 2011 Aug 5.
It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine whether cord blood VDD is associated with FS and whether such association can be modified by genetic variants in a prospective birth cohort.
This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11 ng/ml, and FS as specific IgE ≥ 0.35 kUA/l to any of eight common food allergens in early childhood. We genotyped potentially functional single-nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs.
Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (p(interaction) = 0.003, p(FDR) = 0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR = 1.79, 95%CI: 1.15-2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (p(interaction) = 9 × 10(-6) ).
Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS.
维生素 D 缺乏症（VDD）被认为与食物致敏（FS）进而食物过敏的发生有关。然而，目前的流行病学证据尚存在争议。本研究旨在探讨脐血 VDD 是否与 FS 相关，以及这种相关性是否可被特定基因变异所修饰。
本研究纳入了 649 名于波士顿医疗中心出生的婴儿，对其进行前瞻性随访。我们将 VDD 定义为脐血 25（OH）D＜11ng/ml，FS 定义为在儿童早期特异性 IgE 水平≥0.35kUA/l 且针对 8 种常见食物过敏原中的任意一种。我们对 11 个已知参与 IgE 和 25（OH）D 浓度调节的基因中的潜在功能单核苷酸多态性（SNP）进行了基因分型。采用 logistic 回归分别检验了 VDD 对 FS 的影响以及与 SNP 的联合影响。
在 649 名儿童中，44%存在 VDD，37%存在 FS。单独分析时，VDD 与 FS 无关。与 SNP 联合分析时，我们发现白细胞介素 4 基因多态性（rs2243250）与 VDD 之间存在显著的交互作用（交互作用的 P 值=0.003，错误发现率 FDR 校正值=0.10）：在携带 CC/CT 基因型的儿童中，VDD 增加了 FS 的发病风险（OR=1.79，95%CI：1.15-2.77）。在 MS4A2（rs512555）、FCER1G（rs2070901）和 CYP24A1（rs2762934）基因的 SNP 中观察到类似但较弱的相互作用。当同时考虑这 4 个 SNP 时，存在明显的基因-VDD 交互作用（交互作用的 P 值=9×10（-6））。
我们的数据表明，VDD 可能会增加特定基因型个体 FS 的发病风险，为 FS 相关的基因-维生素 D 相互作用提供了证据。
