Kaur Manreet, Panikkath Deepa, Yan Xiaofei, Liu Zhenqiu, Berel Dror, Li Dalin, Vasiliauskas Eric A, Ippoliti Andrew, Dubinsky Marla, Shih David Q, Melmed Gil Y, Haritunians Talin, Fleshner Phillip, Targan Stephan R, McGovern Dermot P B
*F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California; †Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; ‡Division of Hematology and Oncology, Department of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California; and §Pediatric Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California.
Inflamm Bowel Dis. 2016 Apr;22(4):862-9. doi: 10.1097/MIB.0000000000000705.
Perianal Crohn's Disease (pCD) is a particularly severe phenotype associated with poor quality of life with a reported prevalence of 12%-40%. Previous studies investigating the etiology of pCD have been limited in the numbers of subjects and the intensity of genotyping. The aim of this study was to identify clinical, serological, and genetic factors associated with pCD.
We performed a case-control study comparing patients with (pCD+) and without perianal (pCD) involvement in CD; defined as the presence of perianal abscesses or fistulae. Data on demographics and clinical features were obtained by chart review. Inflammatory bowel disease-related serology was determined by enzyme-linked immunosorbent assay. Genetic data were generated using Illumina genotyping platforms.
We included 1721 patients with CD of which 524 (30.4%) were pCD+ and 1197 were pPCD. pCD was associated with distal colonic disease (Odds ratio 5.54 [3.23-9.52], P < 0.001), stricturing disease behavior (1.44 [1.14-1.81], P = 0.002) and family history of inflammatory bowel disease (4.98 [3.30-7.46], P < 0.001). pCD was associated with higher anti-sacharomyces cerevisae antibodies IgA (P < 0.001) and OmpC (P = 0.008) antibody levels. pCD was associated with known inflammatory bowel disease loci, including KIF3B, CRTC3, TRAF3IP2, JAZF1, NRIP1, MST1, FUT2, and PTGER (all P < 0.05). We also identified genetic association with genes involved in autophagy (DAPK1, P = 5.11 × 10), TNF alpha pathways (NUCB2, P = 8.68 × 10; DAPK1), IFNg pathways (DAPK1; NDFIP2, P = 8.74 × 10), and extracellular matrix and scaffolding proteins (USH1C, P = 8.68 × 10; NDFIP2; TMC07, P = 8.87 × 10). Pathway analyses implicated the JAK-Stat pathway (pc = 3.72 × 10).
We have identified associations between pCD, more distal colonic inflammation, Crohn's disease-associated serologies, and genetic variation in the JAK-Stat pathway.
肛周克罗恩病（pCD）是一种特别严重的表型，与生活质量差相关，报告患病率为12%-40%。既往关于pCD病因的研究在研究对象数量和基因分型强度方面存在局限性。本研究的目的是确定与pCD相关的临床、血清学和遗传因素。
我们进行了一项病例对照研究，比较克罗恩病（CD）患者中有无肛周（pCD）受累（定义为存在肛周脓肿或瘘管）的情况。通过查阅病历获取人口统计学和临床特征数据。采用酶联免疫吸附测定法检测炎症性肠病相关血清学指标。使用Illumina基因分型平台生成遗传数据。
我们纳入了1721例CD患者，其中524例（30.4%）为pCD+，1197例为非pCD。pCD与结肠远端疾病相关（比值比5.54[3.23-9.52]，P<0.001）、狭窄型疾病行为相关（1.44[1.14-1.81]，P=0.002）以及炎症性肠病家族史相关（4.98[3.30-7.46]，P<0.001）。pCD与较高的抗酿酒酵母抗体IgA（P<0.001）和OmpC（P=0.008）抗体水平相关。pCD与已知的炎症性肠病基因座相关，包括KIF3B、CRTC3、TRAF3IP2、JAZF1、NRIP1、MST1、FUT2和PTGER（均P<0.05）。我们还发现了与自噬相关基因（DAPK1，P=5.11×10）、肿瘤坏死因子α通路相关基因（NUCB2，P=8.68×10；DAPK1）、干扰素γ通路相关基因（DAPK1；NDFIP2，P=8.74×10）以及细胞外基质和支架蛋白相关基因（USH1C，P=8.68×10；NDFIP2；TMC07，P=8.87×I0）的遗传关联。通路分析提示JAK-Stat通路（pc=3.72×10）。
我们已经确定了pCD、更广泛的结肠远端炎症、克罗恩病相关血清学指标以及JAK-Stat通路中的基因变异之间的关联。
