A genetic study has extended our understanding of susceptibility to Crohn’s disease, showing that the 5q31 (IBD5) cytokine cluster in British Caucasians does not interact with CARD15 variants and is rare in Japanese people. Nevertheless, potential genetic interactions still remain possible if variants in other susceptibility loci are identified, the researchers say.

IBD5 haplotype showed strong linkage disequilibrium with CD phenotype in a family association based study in British Caucasians. No evidence of genetic interaction between IBD5 haplotype, CARD15 variants, and TNF₋₈₅₇ was identified in stratified transmission disequilibrium tests or log linear analysis. IBD5 haplotype was rare in the Japanese cohort: none was homozygous for the haplotype, preventing further tests.

The researchers performed family based association studies on 282 CD trios identified from the Oxford Gastroenterology Unit, UK, who were screened for IBD5 haplotype, CARD15, and TNF₋₈₅₇ variants. The Japanese cohort contained 178 patients with CD from a hospital in Sendai, Japan, and 156 volunteers acting as controls, who were screened for IBD5 haplotype.

Among Caucasians, variants at three loci are associated with CD: chromosome 5q31 (IBD5), TNF₋₈₅₇, and CARD15/NOD2. Multiple variants are suspected in this disease, with the potential for genetic—epistatic—interaction among them, not just an additive effect. Evidence in a mouse model of IBD has shown that epistatic interactions can occur among loci for susceptibility to colitis.