Acute appendicitis is a common disease with a causative mechanism that is likely multifactorial. Existing evidence^1-4 is suggestive of a familial predisposition to acute appendicitis, with heritability estimates ranging from 27% to 56%. In a multi-institutional genome-wide association study in this issue of JAMA Surgery, Gaitanidis and colleagues⁵ identified a polymorphism at 18q, located in the NEDD4-like E3 ubiquitin protein ligase (NEDD4L) gene, which was associated with the development of acute appendicitis. They validated this finding by demonstrating differential expression of NEDD4L in appendiceal tissue from donors with vs without acute appendicitis. This study⁵ identifies only the second polymorphism known to be associated with acute appendicitis. The locus 4q25, adjacent to the paired-like homeodomain 2 (PITX2) gene, was the first (to our knowledge) to be associated with an increased risk of acute appendicitis.^1,6,7 Within the cohorts analyzed in the study by Gaitanidis et al,⁵ however, 18q demonstrated a larger effect size than 4q25, suggesting the possibility of a more causal link between perturbation of NEDD4L and the pathogenesis of acute appendicitis. These types of polymorphisms may be associated with secretion quality or appendiceal luminal quality that may predispose to appendicitis.

急性阑尾炎是一种常见疾病，其致病机制可能是多因素的。现有证据^{1 -4}提示急性阑尾炎的家族性易感性，遗传率估计范围为 27% 至 56%。在本期JAMA Surgery 的一项多机构全基因组关联研究中，Gaitanidis 及其同事⁵在 18q 处发现了一个多态性，位于 NEDD4 样 E3 泛素蛋白连接酶 ( NEDD4L ) 基因中，该基因与急性阑尾炎。他们通过证明NEDD4L在患有与未患有急性阑尾炎的供体的阑尾组织中的差异表达来验证这一发现。本研究⁵仅识别已知与急性阑尾炎相关的第二种多态性。与成对的同源域 2 ( PITX2 ) 基因相邻的基因座 4q25是第一个（据我们所知）与急性阑尾炎风险增加相关的。^{1 ,6 ,7}在 Gaitanidis 等人的研究中分析的队列中，⁵然而，18q 表现出比 4q25 更大的效应大小，这表明NEDD4L 的扰动与急性阑尾炎的发病机制之间可能存在更多因果关系。这些类型的多态性可能与可能导致阑尾炎的分泌质量或阑尾腔质量有关。