Department of Pediatrics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Division of Allergy and Immunology, University of Cincinnati, Cincinnati, OH, USA.
Genes Immun. 2019 Apr;20(4):281-292. doi: 10.1038/s41435-018-0034-z. Epub 2018 Jun 8.
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by immune hypersensitivity to food. Herein, we tested whether genetic risk factors for known, non-allergic, immune-mediated diseases, particularly those involving autoimmunity, were associated with EoE risk. We used the high-density Immunochip platform, encoding 200,000 genetic variants for major auto-immune disease. Accordingly, 1214 subjects with EoE of European ancestry and 3734 population controls were genotyped and assessed using data directly generated or imputed from the previously published GWAS. We found lack of association of EoE with the genetic variants in the major histocompatibility complex (MHC) class I, II, and III genes and nearly all other loci using a highly powered study design with dense genotyping throughout the locus. Importantly, we identified an EoE risk locus at 16p13 with genome-wide significance (P=2.05 × 10, odds ratio = 0.76-0.81). This region is known to encode for the genes CLEC16A, DEXI, and CIITI, which are expressed in immune cells and esophageal epithelial cells. Suggestive EoE risk were also seen 5q23 (intergenic) and 7p15 (JAZF1). Overall, we have identified an additional EoE risk locus at 16p13 and highlight a shared and unique genetic etiology of EoE with a spectrum of immune-associated diseases.
嗜酸性食管炎（EoE）是一种由食物免疫过敏引起的慢性食管炎。在这里，我们测试了已知的非过敏性免疫介导疾病的遗传风险因素，特别是涉及自身免疫的疾病，是否与 EoE 风险相关。我们使用了高密度免疫芯片平台，该平台编码了 200000 个主要自身免疫性疾病的遗传变异。因此，对 1214 名欧洲血统的 EoE 患者和 3734 名人群对照进行了基因分型，并使用直接从先前发表的 GWAS 中生成或推断的数据进行了评估。我们发现，在主要组织相容性复合体（MHC）I、II 和 III 基因和几乎所有其他基因座中，EoE 与遗传变异没有关联，这是一项具有强大研究设计和整个基因座密集基因分型的研究。重要的是，我们在 16p13 上确定了一个与全基因组显著性相关的 EoE 风险基因座（P=2.05×10，优势比=0.76-0.81）。该区域已知编码 CLEC16A、DEXI 和 CIITI 基因，这些基因在免疫细胞和食管上皮细胞中表达。在 5q23（基因间）和 7p15（JAZF1）也观察到了提示性的 EoE 风险。总体而言，我们在 16p13 上确定了另一个 EoE 风险基因座，并强调了 EoE 与一系列免疫相关疾病具有共同和独特的遗传病因。
