Background

Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development.

Objective

We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home).

Methods

We conducted a case-control study using hospital-based cases (n = 127) and control subjects representative of the hospital catchment area (n = 121). We computed case-only interaction tests and in secondary analyses evaluated the combined and independent effects of genotype and environmental factors on the risk of EoE.

Results

Case-only analyses identified interactions between rs6736278 (CAPN14) and breast-feeding (P = .02) and rs17815905 (LOC283710/KLF13) and NICU admission (P = .02) but not with any of the factors examined. Case-control analyses suggested that disease risk might be modifiable in subjects with certain gene variants. In particular, breast-feeding in those with the susceptibility gene variant at rs6736278 (CAPN14) reduced the risk of EoE (adjusted odds ratio, 0.08; 95% CI, 0.01-0.59). Admission to the NICU in those without the susceptibility gene variant at rs17815905 (LOC283710/KLF13) significantly increased the risk of having disease (adjusted odds ratio, 4.83; 95% CI, 1.49-15.66).

Conclusions

The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.

中文翻译：

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儿童嗜酸性粒细胞性食管炎患者的早期环境暴露与遗传易感性变量相互作用

背景

尽管嗜酸性食管炎（EoE）与某些基因变异有关，但EoE的发病率迅速上升表明环境因素有助于疾病的发展。

客观的

我们测试了易感EoE的多态性（在TSLP，LOC283710 / KLF13，CAPN14，CCL26和TGFB内）与所涉及的早期生命因素（婴儿中使用抗生素，剖宫产，母乳喂养，新生儿重症监护病房之间）之间的基因环境相互作用。[NICU]入场，家里没有宠物）。

方法

我们使用基于医院的病例（n = 127）和代表医院服务区域的对照对象（n = 121）进行了病例对照研究。我们计算了仅案例的交互作用测试，并在次要分析中评估了基因型和环境因素对EoE风险的组合和独立影响。

结果

仅病例分析确定了rs6736278 （CAPN14）与母乳喂养（P  = .02）和rs17815905 （LOC283710 / KLF13）与NICU入院（P  = .02）之间的相互作用，但没有与所考察的任何因素进行交互。病例对照分析表明，患有某些基因变异的受试者的疾病风险可能是可改变的。特别是，在rs6736278 （CAPN14）有易感基因变异的人群中，母乳喂养降低了发生EoE的风险（校正比值比为0.08； 95％CI为0.01-0.59）。rs17815905 （LOC283710 / KLF13）没有易感基因变异的患者入选NICU显着增加了患病的风险（校正比值比，4.83； 95％CI，1.49-15.66）。

结论

基因（CAPN14和LOC283710 / KLF13）与生命早期环境因素（母乳喂养和新生儿重症监护病房（NICU）的进入）之间的相互作用可能会导致EoE易感性。