基因多态性、母乳喂养与儿童早期食物过敏的发展。
Gene polymorphisms, breast-feeding, and development of food sensitization in early childhood.
机构信息
Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL 60614, USA.
出版信息
J Allergy Clin Immunol. 2011 Aug;128(2):374-81.e2. doi: 10.1016/j.jaci.2011.05.007.
BACKGROUND
The effect of breast-feeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
OBJECTIVE
We sought to evaluate the effect of breast-feeding and gene-breast-feeding interactions on food sensitization (FS) in a prospective US birth cohort.
METHODS
This study included 970 children who were prospectively followed since birth. Breast-feeding history was obtained from a standardized questionnaire interview. FS was defined as a specific IgE level of 0.35 kU(A)/L or greater to any of 8 common food allergens. Eighty-eight potentially functional single nucleotide polymorphisms (SNPs) were genotyped from 18 genes involved in innate immunity or T(H)1/T(H)2 balance. Logistic regression models were used to test the effects of breast-feeding and gene-breast-feeding interactions on FS, with adjustment for pertinent covariates.
RESULTS
Children who were ever breast-fed (n = 739), including exclusively breast-fed children, were at a 1.5 (95% CI, 1.1-2.1; P = .019) times higher risk of FS than never breast-fed children (n = 231). This association was significantly modified by rs425648 in the IL-12 receptor β1 gene (IL12RB1; P for interaction = .0007): breast-feeding increased the risk of FS (odds ratio, 2.0; 95% CI, 1.4-3.1; P = .0005) in children carrying the GG genotype but decreased the risk (odds ratio, 0.6; 95% CI, 0.3-1.4; P = .252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the Toll-like receptor 9 (TLR9; rs352140) and thymic stromal lymphopoietin (TSLP; rs3806933) genes. The interaction between the combined genotypes of the 3 SNPs and breast-feeding on FS was even stronger (P for interaction < 10⁻⁵).
CONCLUSION
Our data suggest that the effect of breast-feeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
背景
母乳喂养对过敏性疾病发展的影响尚不确定。目前尚无数据表明这种关系是否因个体基因型而异。
目的
我们旨在评估母乳喂养及其与基因的相互作用对前瞻性美国出生队列中食物过敏（FS）的影响。
方法
本研究纳入了 970 名自出生起即接受前瞻性随访的儿童。通过标准化的问卷调查获取母乳喂养史。FS 定义为对 8 种常见食物过敏原中的任何一种的特异性 IgE 水平为 0.35 kU(A)/L 或更高。对 18 个参与固有免疫或 T(H)1/T(H)2 平衡的基因中的 88 个潜在功能单核苷酸多态性（SNP）进行基因分型。采用 logistic 回归模型，在调整相关协变量的基础上，检验母乳喂养和基因-母乳喂养相互作用对 FS 的影响。
结果
曾进行母乳喂养（n=739）的儿童，包括纯母乳喂养儿童，患 FS 的风险是从未进行母乳喂养儿童（n=231）的 1.5 倍（95%CI，1.1-2.1；P=0.019）。IL-12 受体β1 基因（IL12RB1）rs425648 的存在显著改变了这种关联（基因-母乳喂养相互作用的 P 值=0.0007）：在携带 GG 基因型的儿童中，母乳喂养增加了 FS 的风险（比值比，2.0；95%CI，1.4-3.1；P=0.0005），而在携带 GT/TT 基因型的儿童中，母乳喂养降低了 FS 的风险（比值比，0.6；95%CI，0.3-1.4；P=0.252）。在 Toll 样受体 9（TLR9；rs352140）和胸腺基质淋巴细胞生成素（TSLP；rs3806933）基因中的 SNP 也观察到类似的相互作用。这 3 个 SNP 的联合基因型与母乳喂养对 FS 的相互作用更强（基因-母乳喂养相互作用的 P 值<10⁻⁵）。
结论
我们的数据表明，IL12RB1、TLR9 和 TSLP 基因中的 SNP 单独和共同作用均能修饰母乳喂养对 FS 的影响。我们的研究结果强调了在评估这种关系时考虑个体遗传变异的重要性。
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