Eosinophilic esophagitis (EoE) is a chronic allergic disease associated with marked mucosal eosinophil accumulation. Multiple studies have reported a strong familial component to EoE, with the presence of EoE increasing the risk for other family members with EoE. Epidemiologic studies support an important role for environmental risk factors as modulators of genetic risk. In a small percentage of cases, including patients who have Mendelian diseases with co-occurrent EoE, rare genetic variation with large effect sizes could mediate EoE and explain multigenerational incidence in families. Common genetic risk variants mediate genetic risk for the majority of patients with EoE. Across the 31 reported independent EoE risk loci (P < 10-5), most of the EoE risk variants are located in between genes (36.7%) or within the introns of genes (42.4%). Although some variants do change the amino acid sequence of genes (2.2%), only 3 of the 31 EoE risk loci harbor an amino acid-changing variant. Thus most EoE risk loci are outside of the coding regions of genes, suggesting a key role for gene regulation in patients with EoE, which is consistent with most other complex diseases.

中文翻译：

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嗜酸性粒细胞性食管炎的遗传病因学。


嗜酸性粒细胞性食管炎（EoE）是一种与粘膜嗜酸性粒细胞显着积聚相关的慢性过敏性疾病。多项研究表明 EoE 有很强的家族因素，EoE 的存在会增加其他家庭成员患 EoE 的风险。流行病学研究支持环境风险因素作为遗传风险调节因素的重要作用。在一小部分病例中，包括患有孟德尔疾病并同时发生 EoE 的患者，具有大效应的罕见遗传变异可以介导 EoE 并解释家庭中的多代发病率。常见的遗传风险变异会介导大多数 EoE 患者的遗传风险。在 31 个报告的独立 EoE 风险位点 (P < 10-5) 中，大多数 EoE 风险变异位于基因之间 (36.7%) 或基因内含子内 (42.4%)。尽管一些变异确实改变了基因的氨基酸序列（2.2%），但 31 个 EoE 风险基因座中只有 3 个含有氨基酸改变变异。因此，大多数 EoE 风险位点位于基因编码区之外，这表明基因调控在 EoE 患者中发挥着关键作用，这与大多数其他复杂疾病一致。