UC, like CD, is caused by (largely unknown) environmental factors in a genetically susceptible individual. Of the 163 confirmed IBD genes, 110 loci are associated with both UC and CD; only 23 are UC-specific. Therefore it is not surprising that a family history of IBD increases the risk of developing UC although the life time risk of UC in a 1st degree relative is only 2%. Pathways and gene regions of particular importance in UC are the HLA region, IL23R gene on chromosome 1, DLG5 gene on chromosome 10, the JAK/STAT pathway, MDR-1 gene and TLR genes.
Similarly, pouchitis is thought to occur due to interactions between a host’s immune system and pouch microbiota.
The environmental factors predisposing to UC are similar to CD. They include family history of IBD, infectious gastroenteritis, childhood use of antibiotics, and possibly NSAID use. Prior appendicectomy and tobacco smoking may reduce the chance of susceptible individuals developing UC.