Mei Ling, Targan Stephan R, Landers Carol J, Dutridge Debra, Ippoliti Andrew, Vasiliauskas Eric A, Papadakis Konstantinos A, Fleshner Phillip R, Rotter Jerome I, Yang Huiying
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Gastroenterology. 2006 Apr;130(4):1078-85. doi: 10.1053/j.gastro.2006.02.013.
BACKGROUND & AIMS: Crohn's disease (CD) is a genetically complex disorder with strong familial aggregation. Pathogenesis appears to involve dysregulation of the immune response to endogenous bacteria. Anti-Escherichia coli outer membrane porin C (anti-OmpC) expression reflects an exaggerated response to commensal bacteria and occurs with higher frequency in CD. The aim of this study was to determine whether there is familial aggregation and genetic determination of anti-OmpC expression in CD families.
Study groups consisted of 787 CD patients, 389 ulcerative colitis (UC) patients, 619 unaffected relatives, and 216 healthy controls. Serum anti-OmpC was detected by enzyme-linked immunosorbent assay.
CD patients had a greater percentage of anti-OmpC than UC patients and healthy controls. Anti-OmpC expression was more frequent in unaffected relatives from CD-only or mixed families, compared with healthy controls (P = .002 and .0001, respectively), and it was more frequent in UC patients from mixed families than those from UC-only families (P = .02). There was a significant familiality in anti-OmpC expression: P = .02 for qualitative concordance and P < .0001 for quantitative intraclass correlation. The heritability estimate for anti-OmpC level was .39 (P < .0001).
Anti-OmpC is a heritable immunophenotype. Increased anti-OmpC expression in the unaffected family members of CD patients suggests that anti-OmpC may be an immunologic risk marker for CD. That UC patients in mixed families had a higher response to OmpC than those in UC-only families indicates pathophysiologic heterogeneity within UC.
克罗恩病（CD）是一种具有强烈家族聚集性的基因复杂疾病。其发病机制似乎涉及对内源性细菌免疫反应的失调。抗大肠杆菌外膜孔蛋白C（抗OmpC）表达反映了对共生菌的过度反应，且在CD患者中出现频率更高。本研究旨在确定CD家族中抗OmpC表达是否存在家族聚集性及基因决定性。
研究组包括787例CD患者、389例溃疡性结肠炎（UC）患者、619例未患病亲属和216例健康对照。采用酶联免疫吸附测定法检测血清抗OmpC。
CD患者中抗OmpC的比例高于UC患者和健康对照。与健康对照相比，仅患CD或混合家族中的未患病亲属抗OmpC表达更频繁（分别为P = 0.002和0.0001），且混合家族中的UC患者比仅患UC家族中的UC患者抗OmpC表达更频繁（P = 0.02）。抗OmpC表达存在显著家族性：定性一致性P = 0.02，定量组内相关性P < 0.0001。抗OmpC水平的遗传度估计值为0.39（P < 0.0001）。
抗OmpC是一种可遗传的免疫表型。CD患者未患病家庭成员中抗OmpC表达增加表明抗OmpC可能是CD的一种免疫风险标志物。混合家族中的UC患者比仅患UC家族中的UC患者对OmpC反应更高，这表明UC存在病理生理异质性。
