The aetiology of inflammatory bowel disease (IBD) is unknown but considered to be caused by interplay of genetic and environmental factors.
The aims of this thesis were to study the influence of genetics and environmental factors in aetiology, disease phenotype and levels of Anti-Saccharomyces cerevisiae antibodies (ASCA), as well as to assess whether CARD15/NOD2 polymorphisms explain the influence of genetics in these aspects.
Twin pairs, where at least one twin in each pair had been hospitalized for IBD, were identified using a combination of the Swedish twin registry and the Swedish Hospital Discharge Register. Twin pairs with confirmed IBD were invited to take part in a questionnaire-based study on environmental factors and studies on ASCA and CARD 15/NOD2 polymorphisms.
The follow-up of the old Swedish twin group showed fairly stable concordance rates. A high degree of concordance regarding age at diagnosis, disease location and behaviour was seen in concordant monozygotic twin pairs with Crohn's disease (CD).
The three "classical" CARD15/NOD2 polymorphisms were infrequent in Swedish CD twins and healthy controls, but seemed to be more common among concordant than discordant monozygotic twins with CD.
No increased occurrence of ASCA was observed in healthy twin siblings in discordant monozygotic twin pairs, but a high degree of concordance in ASCA titres was seen in concordant monozygotic twin pairs with CD. ASCA were not associated with CARD15/NOD2.
Including both Swedish and Danish twins, associations between recurrent gastrointestinal infections up to age 20 years and both ulcerative colitis (UC) and CD were observed, whereas coffee and egg consumption was associated with UC only. Swimming in lakes in contrast with swimming pools, sea and rivers was also associated with UC.
These results confirm a stronger genetic influence in CD than in UC and suggest that genetic factors are important not only in acquiring the disease but also in determining disease characteristics of CD. The CARD15/NOD2 variants contribute, but do not fully explain concordance of CD and support the hypothesis that concordant monozygotic twins are under an increased load of susceptibility genes. Furthermore, the results question the concept of ASCA as a marker of genetic susceptibility for CD and we propose that ASCA are a marker of a response to an environmental antigen and that specific gene(s) other than CARD15/NOD2 determine the level of response and perhaps also specific phenotypic characteristics. The results also indicate, that markers of possible infectious events during childhood/adolescence and dietary factors may influence the risk of IBD. In addition, previous reported associations between smoking and IBD were confirmed.
Linköping: Linköping University Electronic Press , 2005. , 76 p.
2005-09-30, Wilandersalen, Universitetssjukhuset i Örebro, Örebro, 09:00 (English)