8 - Genetic Aspects of Inflammatory Bowel Disease

Abstract

SUMMARY Ulcerative colitis and Crohn’s disease are not classic genetically transmitted disorders. Inheritable protein, enzymatic or metabolic defects or chromosomal abnormalities have not been demonstrated. However, the accumulated circumstantial information strongly supports a genetic influence in the pathogenesis of at least 15 to 20 per cent of patients with I.B.D. This evidence includes the multiple family occurrences, usually one, and occasionally two or more additional affected family members. The development of I.B.D. in three or more members of the same family is especially impressive. Two ‘controlled’ studies (Binder et al, 1966; Singer et al, 1971) confirm the significantly increased family incidence of I.B.D. Ulcerative colitis is more likely to occur than Crohn’s disease among the families of probands with ulcerative colitis and the same relationship holds for Crohn’s disease. However, an intermingling of the two disorders is noted in approximately 25 per cent of the familial occurrences. The familial cases more often involve first-degree relatives. Ulcerative colitis also has been documented in eight pairs of monozygotic twins with concordance in five and discordance in three; and in at least six pairs of dizygotic twins. Crohn’s disease, with concordance, has been recorded in at least seven pairs of monozygotic twins. The increased incidence of ankylosing spondylitis, with an established autosomal dominant gene mechanism, among patients with ulcerative colitis and with regional enteritis, further supports a genetic influence in I.B.D. The genetic mechanism involved is not known. Classic mendelian ratios are not observed in affected families. The most likely genetic mechanism is the combined interaction of several genes, the polygenic or multifactoral type of inheritance, interacting with environmental influences to precipitate inflammatory bowel disease in susceptible individuals.