Brant Steven R, Wang Ming-Hsi, Rawsthorne Patricia, Sargent Michael, Datta Lisa Wu, Nouvet Franklin, Shugart Yin Yao, Bernstein Charles N
Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Am J Gastroenterol. 2007 Feb;102(2):313-23. doi: 10.1111/j.1572-0241.2006.00926.x. Epub 2006 Nov 13.
Multiple established Crohn's disease (CD) and ulcerative colitis (UC) risk factors including family history, tobacco use, Jewish ethnicity, urban residency, and CARD15/NOD2 mutations have been evaluated singly and in hospital-based observational studies. The goal of this study was to assess the relative contributions of all these risk factors jointly in a nonreferral, population-based cohort derived from a population epidemiologic database.
CD (N = 232) and UC (N = 121) subjects were ascertained from our population-based IBD Registry derived from Manitoba Health, the single provincial insurer. Healthy controls (HC) (N = 336) were recruited via a 10:1 mailing matched for age, sex, and postal code. Ethnicity, tobacco use, family history, residency, and CARD15/NOD2 genotype status were determined.
In both univariate analyses and analyses adjusted for all risk factors, CD was influenced independently by CARD15/NOD2 heterozygote and homozygote/compound-heterozygote status (adjusted odds ratios [OR] 3.7 and 40.0, respectively), Jewish ethnicity (OR 18.5), CD family history (OR 6.2), and smoking (OR 3.0 current and 1.7 ex-smoker, respectively). Penetrance for homozygote/compound-heterozygotes was 4.9%, heterozygotes 0.54%, and wild types 0.184%. Population attributable risk for CARD15 was 26.7% and current tobacco use was 46.8%. A tobacco-CARD15 interaction was not observed. UC was influenced by Jewish ethnicity (OR 37.1), and by family history (OR 2.6), ex-smoker status (OR 1.9), and CARD15/NOD2 heterozygote or homozygote/compound-heterozygote status (OR 1.9 and 6.4, respectively) in adjusted analyses only.
CARD15/NOD2, family history, smoking, and Jewish ethnicity are independent risk factors for CD. Examination of these risk factors together in a single population-based cohort has provided initial data for population epidemiological characterization and genetic counseling uses.
多种已确定的克罗恩病（CD）和溃疡性结肠炎（UC）风险因素，包括家族史、吸烟情况、犹太族裔、城市居住情况以及CARD15/NOD2突变，已在基于医院的观察性研究中被单独评估。本研究的目的是在一个源自人群流行病学数据库的非转诊、基于人群的队列中，联合评估所有这些风险因素的相对贡献。
从我们基于人群的炎症性肠病登记处确定了CD患者（N = 232）和UC患者（N = 121），该登记处源自曼尼托巴省唯一的省级保险公司曼尼托巴健康保险公司。通过按年龄、性别和邮政编码以10:1的比例进行邮件招募，选取了健康对照（HC）（N = 336）。确定了种族、吸烟情况、家族史、居住情况以及CARD15/NOD2基因型状态。
在单因素分析以及对所有风险因素进行调整后的分析中，CD分别独立受到CARD15/NOD2杂合子和纯合子/复合杂合子状态（调整后的优势比[OR]分别为3.7和40.0）、犹太族裔（OR 18.5）、CD家族史（OR 6.2）以及吸烟（当前吸烟者OR 3.0，既往吸烟者OR 1.7）的影响。纯合子/复合杂合子的外显率为4.9%，杂合子为0.54%，野生型为0.184%。CARD15的人群归因风险为26.7%，当前吸烟的人群归因风险为46.8%。未观察到吸烟与CARD15之间的相互作用。在仅经过调整的分析中，UC受到犹太族裔（OR 37.1）、家族史（OR 2.6）、既往吸烟者状态（OR 1.9）以及CARD15/NOD2杂合子或纯合子/复合杂合子状态（OR（OR分别为1.9和6.4）的影响。
CARD15/NOD2、家族史、吸烟以及犹太族裔是CD的独立风险因素。在一个单一的基于人群的队列中对这些风险因素进行综合考察，为人群流行病学特征描述和遗传咨询应用提供了初步数据。
