CNTNAP3 Copy Number Variation and its Significance in Crohn's Disease / 胃肠病学

ABSTRACT

DNA copy number variation is an important pathogenic factor of human diseases and might be involved in the pathogenesis and pathological process of inflammatory bowel disease (IBD).Aims: To investigate the copy number variation of CNTNAP3 gene and its significance in Crohn''s disease (CD).Methods: A total of 101 active CD patients admitted from Jul.2009 to Dec.2010 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled.Eighty healthy subjects were served as controls.Peripheral blood or intestinal mucosa samples of CD patients were collected, and the copy number variation of CNTNAP3 gene was screened and validated by array-based comparative genomic hybridization (aCGH, n=8) and real-time PCR (n=93);expression of CNTNAP3 encoding protein was determined by ELISA (n=55).Results: A large fragment copy number amplification was revealed by aCGH at chromosome 9p13 region (including CNTNAP3 gene) in untreated CD patients.Real-time PCR confirmed that the copy number of CNTNAP3 gene was amplified in peripheral blood of CD patients, especially steroid-naive patients as compared with the normal controls (208 616.4±126 984.7 and 233 453.3±113 520.8 vs.161 750.2 ±53 940.3, P0.05).Furthermore, the plasma CNTNAP3 level in CD patients with amplified copy number was not correlated with the simplified endoscopic score for CD (P>0.05).Conclusions: Copy number amplification of CNTNAP3 gene might be involved in the pathogenesis of CD in Chinese population.Glucocorticoid treatment and smoking might affect the copy number variation of CNTNAP3 gene.Plasma CNTNAP3 level cannot discriminate CD patients from healthy subjects.Conclusions of this study needs to be further demonstrated and discussed.