Ashley S E, Tan H-T T, Peters R, Allen K J, Vuillermin P, Dharmage S C, Tang M L K, Koplin J, Lowe A, Ponsonby A-L, Molloy J, Matheson M C, Saffery R, Ellis J A, Martino D
Murdoch Childrens Research Institute, Royal Children's Hospital, Australia.
The Hudson Institute, Monash Translational Health Precinct (MTHP), Monash University, Clayton, Australia.
Clin Exp Allergy. 2017 Aug;47(8):1032-1037. doi: 10.1111/cea.12942. Epub 2017 May 21.
Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.
Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy.
We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.
IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy.
食物过敏在全球范围内构成了相当大的公共卫生负担，12个月大婴儿的发病率高达十分之一。目前仅鉴定出少数食物过敏遗传风险变异体。Th2免疫基因IL13是一个非常有可能的遗传候选基因，因为它在B细胞中IgE类别转换的启动过程中起着核心作用。
在此，我们试图研究IL13基因多态性是否与经激发试验证实的IgE介导的食物过敏的发生有关。
我们对来自HealthNuts研究的367例经激发试验证实的食物过敏病例、199例食物致敏耐受病例和156例非食物过敏对照进行了9个IL13“标签”单核苷酸多态性（标签SNP）的基因分型。12个月大的婴儿通过开放式口服食物激发试验进行表型分析。使用针对祖先分层进行调整的Cochran-Mantel-Haenszel检验对SNP进行检测。在一个独立的、位于同一地点的由四个儿科队列组成的样本中进行了重复研究，该样本包括203例食物过敏病例和330例非食物过敏对照。通过反应性临床病史、95%阳性预测值或激发试验来定义重复样本的表型，并进行IL13基因分型。
在发现样本中，IL13 rs1295686与经激发试验证实的食物过敏相关（P = 0.003；OR = 1.75；CI = 1.20 - 2.53）。在重复样本中也检测到了这种关联（P = 0.03，OR = 1.37，CI = 1.03 - 1.82），并且荟萃分析进一步支持了这一结果（P = 0.0006，OR = 1.50）。然而，我们不能排除与食物致敏的关联。rs1295686变异体A等位基因的携带也与血浆总IgE升高有关。
我们首次在两个独立队列中表明，IL13基因多态性rs1295686（与功能变异体rs20541完全连锁不平衡）与经激发试验证实的食物过敏相关。
