Dataset Information

Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China.

ABSTRACT: BACKGROUND Although 90 susceptibility loci of Crohn's disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population remain unknown. This study explored susceptibility genes for CD and pCD in the Han population from South China. MATERIAL AND METHODS In total, 490 patients diagnosed with CD between July 2012 and June 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were included and divided into the CD group (n=240) and the pCD group (n=250). The healthy control group was composed of 260 volunteers. Peripheral blood samples were taken, and single nucleotide polymorphism (SNP) locus sequencing was used to screen for susceptibility loci. SNPs were sequenced using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS Nine SNPs in TNFSF1 on chromosome 9 were associated with CD. Among them, the rs6478106 locus is a risk locus for CD. The distribution frequency of the T allele of the rs6478106 SNP was significantly different between cases and controls (32.49% versus 18.27%, P<0.001). Rs72553867, located in the IRGM gene on chromosome 5, rs4409764, located in the NKX2-3 gene on chromosome 10, and rs3731772, located in the AOX1 gene on chromosome 2, were susceptibility factors for pCD. Nine SNPs located in TNFSF15 on chromosome 9 were related to CD in Han individuals from Southern China. CONCLUSIONS The rs6478106 T allele is associated with the risk of CD in the investigated population. SNPs rs72553867 (IRGM gene), rs4409764 (NKX2-3 gene), and rs3731772 (AOX1 gene) increase the risk of pCD.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6929548 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China.

Zhang Min M Wang Xiaoyan X Jiang Xiaodong X Yang Xiangling X Wen Chuangyu C Zhi Min M Gao Xiang X Hu Pinjin P Liu Huanliang H

Medical science monitor : international medical journal of experimental and clinical research 20191217

BACKGROUND Although 90 susceptibility loci of Crohn's disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population remain unknown. This study explored susceptibility genes for CD and pCD in the Han population from South China. MATERIAL AND METHODS In total, 490 patients diagnosed with CD between July 2012 and June 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were included and divided into the CD group (n=240 ...[more]

PMID: 31844038

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Project description:BackgroundAlthough perianal fistulas occur commonly in pediatric Crohn's disease (CD), evaluations of health services have been limited since no validated claims-based methods exist for identifying cases.ObjectiveTo develop and validate accurate case definitions for perianal fistulas among pediatric patients with CD from administrative claims.MethodsRetrospective cohort study in which we developed and tested candidate case definitions for perianal fistula. Patients (age 5-21 years between 2005-2012) with CD enrolled in Michigan Medicaid with healthcare at University of Michigan were identified via claims. Medical records were obtained from all identified patients, whose entire records were abstracted. Medical record evidence for perianal fistula was considered the "gold standard" against which candidate case definitions were compared. The reference case definition of perianal fistula (ICD9 565.1) and candidate case definitions were evaluated.ResultsOf 843 patients identified via claims, 274 (33%) met CD criteria for inclusion. The true perianal fistula rate among CD patients was 18% (n = 49). The top-performing candidate case definition identified 15% (n = 42), had sensitivity of 77.6%, specificity of 98.2%, positive predictive value (PPV) 90.5%, negative predictive value (NPV) 95.3%, and area under receiver operator characteristic curve (ROC) of 0.88. In contrast, the reference case definition identified 9% (n = 26), sensitivity 51.0%, specificity 99.6%, PPV 96.2%, NPV 90.3%, and had an area under ROC of 0.75.ConclusionsWe demonstrated that it is feasible to use administrative claims data to accurately identify pediatric patients with perianal fistula complications. Claims-based case definitions were found to be highly accurate through medical record review, providing a high degree of confidence for future studies where chart review is not feasible. These claims-based methods can be applied to claims data in other settings for the evaluation of health services utilization as well as to assess the comparative effectiveness of prevention and treatment strategies.

Project description: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.

Project description:The purpose of the study was to determine the overall risk of a permanent stoma in patients with complicated perianal Crohn's disease, and to identify risk factors predicting stoma carriage. A total of 102 consecutive patients presented with the first manifestation of complicated perianal Crohn's disease in our outpatient department between 1992 and 1995. Ninety-seven patients (95%) could be followed up at a median of 16 years after first diagnosis of Crohn's disease. Patients were sent a standardized questionnaire and patient charts were reviewed with respect to the recurrence of perianal abscesses or fistulas and surgical treatment, including fecal diversion. Factors predictive of permanent stoma carriage were determined by univariate and multivariate analysis. Thirty of 97 patients (31%) with complicated perianal Crohn's disease eventually required a permanent stoma. The median time from first diagnosis of Crohn's disease to permanent fecal diversion was 8.5 years (range 0-23 years). Temporary fecal diversion became necessary in 51 of 97 patients (53%), but could be successfully removed in 24 of 51 patients (47%). Increased rates of permanent fecal diversion were observed in 54% of patients with complex perianal fistulas and in 54% of patients with rectovaginal fistulas, as well as in patients that had undergone subtotal colon resection (60%), left-sided colon resection (83%), or rectal resection (92%). An increased risk for permanent stoma carriage was identified by multivariate analysis for complex perianal fistulas (odds ratio [OR] 5; 95% confidence interval [CI] 2-18), temporary fecal diversion (OR 8; 95% CI 2-35), fecal incontinence (OR 21, 95% CI 3-165), or rectal resection (OR 30; 95% CI 3-179). Local drainage, setons, and temporary stoma for deep and complicated fistulas in Crohn's disease, followed by a rectal advancement flap, may result in closing of the stoma in 47% of the time. The risk of permanent fecal diversion was substantial in patients with complicated perianal Crohn's disease, with patients requiring a colorectal resection or suffering from fecal incontinence carrying a particularly high risk for permanent fecal diversion. In contrast, patients with perianal Crohn's disease who required surgery for small bowel disease or a segmental colon resection carried no risk of a permanent stoma.

Dataset Information

Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China.

Publications

Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China.

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