An international team of researchers has announced the discovery of genetic markers linked with ulcerative colitis risk.
The team led by scientists at the University of Pittsburgh School of Medicine say that their findings may be helpful in understanding the biological pathways involved in the disease, and thus may lead to the development of new treatments that specifically target them.
Ulcerative colitis is a chronic, relapsing disorder that causes inflammation and ulceration in the inner lining of the rectum and large intestine. Its most common symptoms are diarrhoea (oftentimes bloody) and abdominal pain.
Just like Crohn's disease, another chronic gastrointestinal inflammatory disorder, ulcerative colitis is also known as a major form of inflammatory bowel disease (IBD).
"Ulcerative colitis and Crohn's disease are chronic conditions that impact the day-to-day lives of patients," Nature magazine quoted senior author of the study Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh School of Medicine and Graduate School of Public Health, as saying.
"IBD is most often diagnosed in the teenage years or early adulthood. While patients usually don't die from IBD, affected individuals live with its debilitating symptoms during the most productive years of their lives," the researcher added.
With a view to finding factors specific for ulcerative colitis, the researchers performed a genome-wide association study of hundreds of thousands of genetic markers using DNA samples from 1,052 individuals with ulcerative colitis and pre-exisiting data from 2,571 controls, all of European ancestry and residing in North America.
The team said that several genetic markers on chromosomes 1p36 and 12q15 showed highly significant associations with ulcerative colitis, and the association evidence was replicated in independent European ancestry samples from North America and southern Italy.
According to them, nearby genes implicated as possibly playing a role in ulcerative colitis include the ring finger protein 186 (RNF186), OTU domain containing 3 (OTUD3), and phospholipase A2, group IIE (PLA2G2E) - genes on chromosome 1p36, and the interferon, gamma (IFNG), interleukin 26 (IL26), and interleukin 22 (IL22) genes on chromosome 12q15. RNF186 and OTUD3 are members of gene families involved in protein turnover and diverse cellular processes. PLA2G2E, IFNG, IL26 and IL22 are known to play a role in inflammation and the immune response.
The researchers also found highly suggestive associations between ulcerative colitis and genetic markers on chromosome 7q31 within or near the laminin, beta 1 (LAMB1) gene, which is a member of a gene family known to play a role in intestinal health and disease, and confirmed previously identified associations between ulcerative colitis and genetic variants in the interleukin 23 receptor (IL23R) gene on chromosome 1p31 and the major histocompatibility complex on chromosome 6p21.
"My laboratory is focused on studying the genetic basis for IBD. Through genetic mapping, we and our collaborators are successfully identifying regions of the genome that contain IBD genes. The next steps are to understand the functional significance of IBD-associated genetic variants, and then to develop new treatments that specifically target biological pathways implicated by the genetic discoveries. The overall goal of this work is to improve the lives of the millions of patients worldwide that suffer from IBD," said Dr. Duerr.
The study has been reported in the journal Nature Genetics.