Genetic and environmental factors as predictors of disease severity and extent at time of diagnosis in an inception cohort of inflammatory bowel disease, Copenhagen County and City 2003-2005.
2008
Abstract Background and aims The etiology of the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to investigate the influence of genetic, serological, and environmental factors on phenotypic presentation of IBD at diagnosis in a population-based Danish inception cohort from 2003–2005. Methods Three-hundred-forty-seven (62%) of 562 cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients answered a questionnaire concerning environmental factors with possible influence on IBD. Results Fourteen percent of CD patients vs. 11% of controls were positive for common CARD15 mutation (ns), whereas more CD patients than healthy controls were homozygous for the OCTN-TC haplotype ( p =0.03). ASCA was more common in CD (22%) than UC (14%) ( p =0.045) and was related to age and localization of CD. p-ANCA was more frequent in UC ( p =0.00001) but was related to pure colonic CD ( p =0.0001). Sugar consumption was significantly higher in CD patients than in UC patients ( p =0.0001) and more CD patients than UC patients had undergone appendectomy prior to IBD diagnosis ( p =0.03). A possible relation between tonsillectomy and disease severity in CD, and a relation between use of oral contraception and disease localization of UC to rectum/left-sided colon were found. Conclusions In this cohort of unselected IBD patients we found a very low frequency of mutations in IBD susceptibility genes and observed a greater impact of ASCA and ANCA than of genetic factors on disease phenotypes. In addition, several environmental factors seemed to influence disease occurrence and disease presentation in both UC and especially CD.
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