The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant.
1 gene associated with CD has been identified: NOD2/CARD15.
2 independent genome-wide scans found significant evidence and suggestive evidence for linkage on locus 14q11-12, also known as the IBD4 locus.
As part of an ongoing international collaborative effort the IBD International Genetics Consortium undertook a study to further characterize this locus.
The researchers assessed gene-environment interaction (IBD4 x smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs.
The researchers enrolled a total of 733 IBD families, comprising 892 affected sibling pairs.
The investigators genotyped all participants for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus.
| Researchers observed maximum linkage for crohn's disease at marker D14S261|
|Inflammatory Bowel Disease|
The research team evaluated information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location.
The researchers found a significant distortion in the mean allele sharing (MAS) between affected siblings for crohn's disease patients only at each of the 4 markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively).
The research team observed maximum linkage for crohn's disease at marker D14S261.
In addition, the researchers noted that MAS was higher in crohn's disease families in which all siblings or at least one sibling smoked compared with nonsmoking CD families.
Dr Pierik concluded, "The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for crohn's disease and also showed evidence for a gene-environment interaction at this locus."
"Further studies are needed to explore the mechanism by which smoking influences IBD4."