全基因组关联研究确定了四个新的嗜酸性粒细胞性食管炎基因座。

GWAS identifies four novel eosinophilic esophagitis loci.

作者信息

Sleiman Patrick M A, Wang Mei-Lun, Cianferoni Antonella, Aceves Seema, Gonsalves Nirmala, Nadeau Kari, Bredenoord Albert J, Furuta Glenn T, Spergel Jonathan M, Hakonarson Hakon

机构信息

1] The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA [2] Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania 19104, USA.

1] Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania Philadelphia, Philadelphia, Pennsylvania 19104, USA [2] Division of GI, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

出版信息

Nat Commun. 2014 Nov 19;5:5593. doi: 10.1038/ncomms6593.

DOI:10.1038/ncomms6593

PMID:25407941

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4238044/

Abstract

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune diseases, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the oesophagus. The identification of five EoE loci, not only expands our aetiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, oesophageal inflammation and remodelling.

摘要

嗜酸性食管炎（EoE）是一种过敏性疾病，其特征是嗜酸性粒细胞浸润食管。我们之前曾报道过TSLP/WDR36基因座与EoE的关联。在此，我们报告了另外四个基因座的全基因组显著关联；c11orf30和STAT6，它们之前已与特应性疾病和自身免疫性疾病相关联，以及两个EoE特异性基因座，ANKRD27可调节黑素生成酶向表皮黑素细胞的转运，CAPN14编码一种钙蛋白酶，其表达在食管中高度富集。五个EoE基因座的鉴定，不仅扩展了我们对该疾病病因的理解，还可能代表了治疗EoE最使人衰弱的方面——食管炎症和重塑的新治疗靶点。