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Genetic, Serological, and Environmental Factors in
Inflammatory Bowel Disease
A Danish Inception Cohort


Ida Vind  


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Accepted by: of Health Sciences of Copenhagen
Defended on: April 28, 2006
Official opponents: Overlæge, professor, dr.med. Henrik Toft Sørensen , Overlæge, ph.d. Jens Kjeldsen , Overlæge, professor, dr.med. Jørgen Rask Madsen
Tutors: Overlæge ,professor, dr.med. Flemming Bendtsen , Overlæge, dr.med. Pia Munkholm

Published in the PhD Database: April 17, 2009


English abstract
During a two year period from 2003-2005, 562 inflammatory bowel disease (IBD) patients, children and adults, residing in Copenhagen County and City were diagnosed with IBD; of these 209 had Crohn¿s disease (CD), 326 ulcerative colitis (UC) and 27 indeterminate colitis (IC). Increasing incidences of both CD and UC were observed among adults, whereas in children <15 CD increased while UC remained unchanged. Significantly shortening of time from onset of symptoms until diagnosis and decreasing surgery rates were observed among both CD and UC patients compared to previous observations in Copenhagen County. Demographic characteristics and disease extent at the time of diagnosis remained constant compared with previous cohorts.
Demonstration of low frequencies of susceptibility genes among unselected patients illustrated the minor role of these in the characterization of disease phenotypes at the time of diagnosis.
In spite of low prevalence of ASCA in CD patients, associations with age <40 years, small bowel disease, and disease severity were demonstrated. p-ANCA was more common in UC patients. No relation with UC phenotypes were observed, but positive p-ANCA was related to colonic CD.
To emphasize the supposed less important role of genetic susceptibility in sporadic CD, CARD15 frequencies were investigated in Denmark that has a high incidence of CD and in Portugal that has a low CD incidence in order to investigate whether a ¿CARD15 gradient¿ existed accordingly, but no such genetic gradient could be demonstrated.
Other factors, e.g. environmental factors, may play a causative role in the aetiology of IBD.
Patients from the inception cohort answered a questionnaire concerning various environmental factors. Smoking, appendectomy and high carbohydrate consumption were shown to be significantly different in CD and in UC patients. There were more smokers among CD patients, whereas ex-smokers were predominant among UC patients. CD patients had undergone appendicectomy at least one year prior to diagnosis more frequently than had UC patients, and CD patients were demonstrated to have a higher sugar intake than UC patients.
In UC patients, an association between current usage of oral contraceptives and localization of UC to rectum/left-sided colon was observed, and an association between severity of CD and absence of tonsillectomy.



Danish abstract
I perioden 2003-2005 fik 562 patienter, boende i Københavns Amt og Hovedstadsområdet, konstateret inflammatorisk tarmsygdom. 209 personer havde Mb. Crohn (CD), 326 colitis ulcerosa (UC) og 27 indeterminate colitis (IC). Sammenlignet med tidligere undersøgelser fandtes blandt voksne stigende forekomst af både CD og UC, hvorimod der blandt børn <15 år alene var stigende forekomst af CD, men uændret forekomst af UC. Tiden fra første symptom til diagnose og hyppigheden af kirurgi indenfor første år var signifikant mindre end i tidligere studier i Københavns Amt. Demografiske karakteristika og sygdomsudbredning ændrede sig ikke.
I denne gruppe af uselekterede patienter konstateredes lav hyppighed af de undersøgte gener, der øger følsomheden for udvikling af IBD, hvilket illustrerer, at disse gener ikke har væsentlig indflydelse på sygdommenes fænotyper på diagnosetidspunktet.
På trods af lav forekomst af ASCA blandt CD patienter, fandtes sammenhæng mellem alder <40 år, tyndtarmsaffektion og sygdomssværhedsgrad. p-ANCA var hyppigere blandt patienter med UC, men på trods heraf kunne der ikke påvises sammenhæng mellem positiv p-ANCA og sygdomsfænotyper. Dog var der relation mellem positiv p-ANCA og colon CD.
For at understrege den formentlig mindre væsentlige rolle genetisk følsomhed spiller for udvikling af sporadisk IBD, undersøgtes frekvensen af CARD15 mutationer i en dansk population, hvor der er dokumenteret høj hyppighed af IBD, og i en køns- og aldersmatchet portugisisk, hvor der er dokumenteret lav hyppighed af IBD, for at undersøge om der var en eventuel ¿CARD15 gradient¿, hvilket ikke var tilfældet.
Miljøfaktorer formodes at spille en væsentlig rolle i udviklingen af IBD. Patienterne fra den uselekterede kohorte svarede på et spørgeskema, der omhandlede forskellige miljøfaktorer. Rygning, appendektomi og højt sukkerforbrug var signifikant forskellige i grupperne CD og UC. Der var flere rygere blandt CD patienterne, hvorimod tidligere rygerne var i overtal blandt UC patienterne. CD patienterne havde hyppigere fået foretaget appendektomi mindst et år før diagnosen var stillet end UC patienterne, og højt sukker forbrug var også hyppigere blandt patienter med CD.
Blandt de kvindelige UC patienter var der sammenhæng mellem forbrug af p-piller og lokalisation til rectum eller venstre side af colon. Desuden fandtes signifikant sammenhæng mellem sværhedsgraden af patienternes sygdom og fravær af tonsillektomi.