title: Association of inflammatory bowel disease with indicators for childhood antigen and infection exposure.
abstract: OBJECTIVE
  Genetic susceptibility plays an important role in the predisposition to inflammatory bowel disease (IBD), but genetics alone cannot explain the six- to eightfold rise in incidence accompanying postwar socioeconomic changes in developed countries. It is presently unclear how environmental factors either trigger or modify the risk for and course of IBD in the presence of genetic susceptibility.
  
  
  METHODS
  We evaluated 2,351 consecutive responses from IBD patients and from 3,364 of their unaffected first-degree relatives (parents/siblings) who completed a multi-item questionnaire with their physicians as part of a study of IBD genetics. All single-patient families were excluded from the analysis to avoid ascertainment bias, resulting in 120-133 independent cases for the analysis of environmental factors and 1,685 patients to be included in the analysis of birth rank.
  
  
  RESULTS
  No statistically significant association was observed between the presence of IBD and the availability of either (warm) tap water, water toilets, or central heating during childhood. However, higher birth rank (> or =3) was significantly associated with a lower risk of IBD (odds ratio 0.68).
  
  
  CONCLUSIONS
  Lower birth rank as a possible indicator of increased childhood infection exposure was associated with a higher risk for IBD. Future studies need to address the interaction of known genetic variations (e.g., in the NOD2 gene) with environmental factors potentially mediating this effect.
authors.affiliation: First Department of Medicine, Christian Albrecht University, Schittenhelmstrasse 12, 24105 Kiel, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heymann
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D001722:Birth Order; D016022:Case-Control Studies; D015984:Causality; D004777:Environment; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006361:Heating; D006798:Housing; D006801:Humans; D006920:Hygiene; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology* / Q000235:genetics; D010290:Parents; D012307:Risk Factors; D012499:Sanitation; D035781:Siblings; D011795:Surveys and Questionnaires; D014038:Toilet Facilities; D014881:Water Supply