UC San Diego

Background

The α7-subunit of the α7-nicotinic acetylcholine receptor (α7-nAChR) is an obligatory intermediate for the anti-inflammatory effects of the vagus nerve. But in humans, there exists a second gene called CHRFAM7A that encodes a dominant negative α7-nAChR inhibitor. Here, we investigated whether their expression was altered in inflammatory bowel disease (IBD) and colon cancer.

Methods

Quantitative RT-PCR measured gene expression of human α7-nAChR gene (CHRNA7), CHRFAM7A, TBC3D1, and actin in biopsies of normal large and small intestine, and compared to their expression in biopsies of ulcerative colitis, Crohn's disease, and colon cancer.

Results

qRT-PCR showed that CHRFAM7A and CHRNA7 gene expression was significantly (p < .02) up-regulated in IBD (N = 64). Gene expression was unchanged in colon cancer. Further analyses revealed that there were differences in ulcerative colitis and Crohn's Disease. Colon biopsies of ulcerative colitis (N = 33) confirmed increased expression of CHRFAM7A and decreased in CHRNA7 expression (p < 0.001). Biopsies of Crohn's disease (N = 31), however, showed only small changes in CHRFAM7A expression (p < 0.04) and no change in CHRNA7. When segregated by tissue source, both CHRFAM7A up-regulation (p < 0.02) and CHRNA7 down-regulation (p < 0.001) were measured in colon, but not in small intestine.

Conclusion

The human-specific CHRFAM7A gene is up-regulated, and its target, CHRNA7, down-regulated, in IBD. Differences between ulcerative colitis and Crohn's disease tie to location of disease.

Significance

The appearance of IBD in modern humans may be consequent to the emergence of CHRFAM7A, a human-specific α7-nAChR antagonist. CHRFAM7A could present a new, unrecognized target for development of IBD therapeutics.