Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Journal of Negative Results in Biomedicine

Susan Galandiuk²  E Brooks Weller²  Robert Petras³  Shesh N Rai¹  Jianmin Pan¹  Henry Roberts²  Clayton Weller²  Surriya Ahmad²  Maurice R Eichenberger²  Ziad M Kanaan² 

[1] The Department of Bioinformatics and Biostatistics, University of Louisville School of Medicine, 505 S. Hancock St., Louisville, KY 40202, USA;Department of Surgery, The Price Institute of Surgical Research and the Section of Colorectal Surgery, University of Louisville School of Medicine, 550 S. Jackson St, Louisville, KY 40292, USA;AmeriPath Institute of Gastrointestinal Pathology and Digestive Disease, Oakwood village, OH 44146, USA

关键词: IGR;    OCTN1;    IL23r;    NOD2;    SNP;    Ulcerative Colitis;    Crohn's disease;    Inflammatory bowel disease;   

Others  :  820525
DOI  :  10.1186/1477-5751-11-7

 received in 2011-09-19, accepted in 2012-01-23,  发布年份 2012

【 摘 要 】

Background

Crohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America.

Methods

Patients were diagnosed to have CD or UC using conventional radiologic, endoscopic, and/or histopathologic findings. Histological diagnosis was made by a single specialist gastrointestinal pathologist with a particular interest in IBD. Information regarding cigarette smoke exposure was obtained by administration of the Behavioral Risk Factor Surveillance System Survey (BRFSS) to all patients. Genomic DNA was extracted from peripheral blood leukocytes, and polymerase chain reaction (PCR) amplification and genotyping were performed for 11 Single Nucleotide Polymorphisms (SNP) in NOD2, IL23r, OCTN1 genes along with IGR.

Results

Our cohort consists of 1196 patients: 435 controls, 485 CD patients, and 276 UC patients. Only patients with genotype data for at least 7 of 11 SNPs were included in our data analysis. The control groups for all 11 SNPs were in Hardy-Weinberg Equilibrium. In genotype-association SNP analysis, all NOD2 SNPs (rs5743293, rs2066844, rs2066845) and the IL23r SNP (rs11465804) showed a significant association to IBD (p < 0.03). A multiple gene-interaction analysis showed an association between NOD2 and IL23r with UC (p = 0.04). There were no associations between any OCTN1 and IGR SNPs and IBD in this cohort. A multivariable logistic regression analysis showed that female gender, "current" or "former" smoking status, family history of IBD, and NOD2 SNP minor alleles were associated with CD.

Conclusion

IBD remains to be challenging to properly diagnose, characterize, and treat. Our study proposes a combined genetic, phenotypic, and environmental approach in an attempt to better understand IBD. Previously demonstrated associations between OCTN1 and IGR and IBD were not confirmed.

【 授权许可】

   
2012 Kanaan et al; licensee BioMed Central Ltd.

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