Link between inflammatory bowel disease ulcerative colitis and a gene that makes certain cell surface proteins located to a variant amino acid in a key binding site that profoundly influences immune response to antigens, including gut bacteria, reports a team of researchers at the University of Pittsburgh, Cleveland Clinic, Carnegie Mellon University and Harvard Medical School. They published the findings today in the online version of Genes & Immunity.
Variations in genes that regulate immune responses in a region of chromosome 6 have long been linked with susceptibility for many infectious and chronic inflammatory conditions, including ulcerative colitis, said Richard H. Duerr, M.D., professor of medicine, Pitt School of Medicine, co-director and scientific director, UPMC Inflammatory Bowel Disease Center, and the corresponding author of the study. Ulcerative colitis is characterized by recurrent inflammation of the large intestine that results in diarrhea mixed with blood and abdominal pain.
Ulcerative Colitis
Ulcerative colitis is characterized by bouts of diarrhea, bleeding per rectum and pain, which remits and relapses. Fulminant colitis is a possibility, which may require colectomy.
"We tested more than 10,000 points, called single nucleotide polymorphisms, or SNPs, in the gene sequence in this chromosomal region, and we also tested amino acid variations in human leukocyte antigen (HLA) proteins that were deduced from the SNPs to identify those most important for ulcerative colitis," Dr. Duerr said. "Refining the gene association signals in this region enabled us to better understand the underlying mechanisms of the disease."
"This particular position probably plays a significant role in determining the human immune response to extracellular antigens," Dr. Duerr said. "It ties into theories that ulcerative colitis might result from an abnormal immune response to gastrointestinal bacterial antigens or might be an autoimmune disorder caused by an abnormal immune response to a self-antigen."
The researchers also looked for a similar relationship between that amino acid position and Crohn's disease, another chronic inflammatory bowel condition, but did not find a strong association. Still, variants in immune response genes on chromosome 6 likely contribute not only to ulcerative colitis and Crohn's disease, but also to other immune-mediated diseases such as rheumatoid arthritis and multiple sclerosis, added Jean-Paul Achkar, M.D., Department of Gastroenterology & Hepatology, Cleveland Clinic Digestive Disease Institute, an alum of the gastroenterology and hepatology training program at UPMC, and first author of the study.
Source: Eurekalert
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