The Price Institute of Surgical Research and the Section of Colon and Rectal Surgery, Department of Surgery, University of Louisville, Louisville, KY 40292, USA.
Dig Surg. 2012;29(2):107-14. doi: 10.1159/000335745. Epub 2012 Mar 22.
To investigate genotype-phenotype correlations in patients with perianal Crohn's disease (PCD) in order to determine which factors predispose to development of perianal disease in Crohn's patients.
Seven-hundred and ninety-five Caucasian individuals (317 CD patients and 478 controls without inflammatory bowel disease, IBD) were prospectively enrolled into a clinical/genetic database. Demographic and clinical data, as well as peripheral blood leukocyte DNA were obtained from all patients. The following were evaluated: three NOD2/CARD15 polymorphisms: R702W, G908R, and 1007insC; five IL-23r risk alleles: rs1004819, rs10489629, rs2201841, rs11465804, and rs11209026; a well-characterized single-nucleotide polymorphism (SNP) on the IBD5 risk haplotype (OCTN1) and two peripheral tag SNPs (IGR2060 and IGR3096).
PCD occurred in 147 (46%) of CD patients. There was no significant difference in the age at disease diagnosis between non-PCD and PCD patients (33 vs. 29 years, respectively). PCD patients were more likely to have disease located in the colon and ileocolic regions (79 PCD vs. 57% non-PCD; n = 116 vs. n = 96; p < 0.001), whereas patients with non-PCD were more likely to have Crohn's within the terminal ileum and upper gastrointestinal tract (43% non-PCD vs. 21% PCD; n = 73 vs. n = 31; p < 0.05). Thirty-four percent of patients with PCD required a permanent ileostomy (n = 50) compared to only 4% of non-PCD patients (n = 6; p < 0.05). Mutations in CARD15/NOD2 and IL-23r were risk factors for CD overall; however, in contrast to prior reports, in this patient population, OCTN1 and IGR variations within the IBD5 haplotype were not significant predictors of PCD.
Colon/ileocolic CD location appears to be a significant predictor of perianal manifestations of CD. Patients with PCD are more likely to require permanent fecal diversion. We did not identify any genetic variations or combination of clinical findings and genetic variations within the CARD15/NOD2, IL-23r, and OCTN1 genes or IGR that were predictive of PCD.
研究肛周克罗恩病（PCD）患者的基因型-表型相关性，以确定哪些因素易导致克罗恩病患者发生肛周疾病。
795 名白种人（317 名 CD 患者和 478 名无炎症性肠病[IBD]的对照者）前瞻性地纳入临床/遗传数据库。从所有患者中获得人口统计学和临床数据以及外周血白细胞 DNA。评估内容如下：三个 NOD2/CARD15 多态性：R702W、G908R 和 1007insC；五个 IL-23r 风险等位基因：rs1004819、rs10489629、rs2201841、rs11465804 和 rs11209026；IBD5 风险单倍型（OCTN1）上的一个特征明确的单核苷酸多态性（SNP）和两个外周标记 SNP（IGR2060 和 IGR3096）。
147 名（46%）CD 患者发生 PCD。非 PCD 和 PCD 患者的疾病诊断年龄无显著差异（分别为 33 岁和 29 岁）。PCD 患者更有可能出现结肠和回结肠区域的疾病（79 名 PCD 患者 vs. 57%非 PCD 患者；116 名 vs. 96 名；p<0.001），而非 PCD 患者更有可能出现末端回肠和上消化道的克罗恩病（43%非 PCD 患者 vs. 21%PCD 患者；73 名 vs. 31 名；p<0.05）。34%的 PCD 患者需要永久性回肠造口术（50 名患者），而非 PCD 患者仅为 4%（6 名患者）（p<0.05）。CARD15/NOD2 和 IL-23r 突变是 CD 的总体危险因素；然而，与先前的报告相反，在该患者人群中，IBD5 单倍型内的 OCTN1 和 IGR 变异不是 PCD 的显著预测因子。
结肠/回结肠 CD 部位似乎是 CD 肛周表现的重要预测因子。PCD 患者更有可能需要永久性粪便分流。我们没有发现任何遗传变异或 CARD15/NOD2、IL-23r 和 OCTN1 基因内的遗传变异组合或 IGR 可预测 PCD。
