Maternal imprinting and female predominance in familial Crohn's disease

Although the genetic risk factors for familial and sporadic inflammatory bowel disease (IBD) seem identical, the relative risk for contracting IBD in the familial setting is larger as that seen in the population at large, suggesting an important role of epi- and/or paragenetic factors in familial IBD. Epidemiological data indicate a female predominance in IBD, but how this relates to familial IBD has not been assessed.

Familial IBD patients (N=608) were compared with a cohort of 415 sporadic IBD patients with regards to the patterns of sex and disease type distribution. The imprinting pattern in 87 families in which both a parent and a child had IBD was tested using Galton binominal statistics.

The percentage of females in familial IBD population was significantly higher (61%; female/male ratio 1.5) compared with sporadic IBD (54%; female/male ratio 1.2; p=0.011). The analysis of offspring sex distribution pattern revealed significantly higher female to female transmission compared with female to male transmission rate (36 vs. 18, respectively; p=0.02). A significantly higher number of mother to child transmissions (55 vs. 32 of father to child transmissions) was observed (p=0.018). The female imprinting was specifically related to Crohn's disease (31 vs. 14 mother vs. father to child transmissions, respectively; p=0.016).

We propose that a female sex-specific epigenetic inheritance pattern for Crohn's disease is a major contributing factor in the family-specific risk in Crohn's disease. Sex-specific manifestation of familial Crohn's disease can partly explain the epidemiologically observed increased relative risk for females for contracting IBD.