Background

Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. Thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14) genetic variations contribute to EoE, but how this relates to atopy is unclear.

Objective

The purpose of this study was to explore the relationship between EoE, atopy, and genetic risk.

Methods

EoE-atopy enrichment was tested by using 700 patients with EoE and 801 community control subjects. Probing 372 single nucleotide polymorphisms (SNPs) in 63 atopy genes, we evaluated EoE associations using 412 nonatopic and 868 atopic disease control subjects. Interaction and stratified analyses of EoE-specific and atopy-related SNPs were performed.

Results

Atopic disease was enriched in patients with EoE (P < .0001). Comparing patients with EoE and nonatopic control subjects, EoE associated strongly with IL-4/kinesin family member 3A (IL4/KIF3A) (P = 2.8 × 10⁻⁶; odds ratio [OR], 1.87), moderately with TSLP (P = 1.5 × 10⁻⁴; OR, 1.43), and nominally with CAPN14 (P = .029; OR, 1.35). Comparing patients with EoE with atopic disease control subjects, EoE associated strongly with ST2 (P = 3.5 × 10⁻⁶; OR, 1.77) and nominally with IL4/KIF3A (P = .019; OR, 1.25); TSLP's association persisted (P = 4.7 × 10⁻⁵; OR, 1.37), and CAPN14's association strengthened (P = .0001; OR, 1.71). Notably, there was gene-gene interaction between TSLP and IL4 SNPs (P = .0074). Children with risk alleles for both genes were at higher risk for EoE (P = 2.0 × 10⁻¹⁰; OR, 3.67).

Conclusions

EoE genetic susceptibility is mediated by EoE-specific and general atopic disease loci, which can have synergistic effects. These results might aid in identifying potential therapeutics and predicting EoE susceptibility.

中文翻译：

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嗜酸性食管炎（EoE）遗传易感性是由EoE特异性和一般性特应性疾病基因座之间的协同相互作用介导的

背景

嗜酸性食管炎（EoE）是一种与特应性疾病相关的食道炎性疾病。胸腺基质淋巴细胞生成素（TSLP）和钙蛋白酶14 （CAPN14）的遗传变异有助于EoE，但尚不清楚其与特应性的关系。

客观的

这项研究的目的是探讨EoE，特应性疾病和遗传风险之间的关系。

方法

通过使用700例EoE患者和801个社区对照受试者来测试EoE抗体的富集。探索了63个特应性基因中的372个单核苷酸多态性（SNP），我们使用412个非特应性疾病和868个特应性疾病控制对象评估了EoE关联。进行了相互作用和对EoE特异性和特应性相关SNP的分层分析。

结果

EoE患者的特应性疾病丰富（P  <.0001）。比较EoE患者和非特应性对照患者，EoE与IL-4 /驱动蛋白家族成员3A（IL4 / KIF3A）密切相关（P  = 2.8×10 ^-6；优势比[OR]为1.87），与TSLP中等（P  = 1.5×10 ^-4；或，1.43），并使用CAPN14标称值（P  = .029；或，1.35）。将EoE患者与特应性疾病控制对象进行比较，EoE与ST2密切相关（P  = 3.5×10 ^-6； OR为1.77），名义上与IL4 / KIF3A相关（P  = .019; OR，1.25）; TSLP的关联持续存在（P  = 4.7×10 ^-5；或，1.37），而CAPN14的关联增强（P  = .0001；或，1.71）。值得注意的是，TSLP和IL4 SNP之间存在基因-基因相互作用（P  = .0074）。两种基因均具有风险等位基因的儿童发生EoE的风险更高（P  = 2.0×10 ^-10；或，3.67）。

结论

EoE遗传易感性是由EoE特异性和一般性特应性疾病基因座介导的，它们可能具有协同作用。这些结果可能有助于确定潜在的治疗方法并预测EoE敏感性。