Navigation Links
Team pinpoints amino acid variation in immune response gene linked with ulcerative colitis
Date:12/15/2011

PITTSBURGH, Dec. 15 The association between the inflammatory bowel disease ulcerative colitis and a gene that makes certain cell surface proteins has been pinpointed to a variant amino acid in a crucial 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.

"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."

Using sophisticated association techniques, the authors confirmed that an HLA gene called DRB1, which codes for a protein that is involved in the immune response and routinely tested in tissue matching for organ transplantation, was uniquely related to ulcerative colitis. Variation, or polymorphism, in that gene altered which amino acid was selected for the 11th position in the DRB1 protein a key location because it is in a pocket of the so-called binding cleft where other proteins, such as antigens or markers of foreign cells, attach.

"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.


'/>"/>
Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related medicine news :

1. Expert Panel Pinpoints Environmental Culprits in Breast Cancer
2. Study of golf swings pinpoints biomechanical differences between pros and amateurs
3. Project Achilles pinpoints vulnerabilities in ovarian cancer
4. York U study pinpoints part of brain that suppresses instinct
5. Ultrasensitive detector pinpoints big problem in tiny fetal heart
6. Too Much Acetaminophen Over Time May Damage Liver
7. Maypros Japanese partner, Amino Up Chemical, opens new production facility
8. Study links acetaminophen to lower prostate cancer risk
9. Drugmakers to End Infant Formulas of Products With Acetaminophen
10. FDA Lowers Amount of Acetaminophen Allowed in Prescription Painkillers
11. Acetaminophen use in adolescents linked to doubled risk of asthma
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/23/2017)... ... February 23, 2017 , ... On ... issued a letter to withdraw previous guidance issued by the Obama ... The guidance issued in May 2016 by the Obama Administration came in response ...
(Date:2/23/2017)... ... February 23, 2017 , ... Los Angeles-based weight loss surgeon Michael Feiz, M.D., ... From Not to Hot,” which will begin airing on February 24, 2017. The show ... from the 2012 reality television series, “Here Comes Honey Boo Boo.” The earlier series ...
(Date:2/23/2017)... ... ... Dr. David Mahon leads Siena Dental, a comprehensive dental practice located at 10075 ... Patient Rated Henderson Dentist by Find Local Doctors earlier this year. ... who have earned high ratings and superior patient reviews from multiple credible sources. , ...
(Date:2/23/2017)... ... February 23, 2017 , ... The Center ... Rhode Island Consortium for Autism Research and Treatment (RI-CART) and Cinemaworld to present ... spectrum disorder (ASD) to see films in an environment that accommodates their unique ...
(Date:2/23/2017)... ... February 23, 2017 , ... HealthPostures, the desk for standing ... sit stand solutions representative to the Minneapolis Home and Garden Show which is being ... that is garnering national attention is the Minneapolis Convention Center. , From its ...
Breaking Medicine News(10 mins):
(Date:2/23/2017)... , Feb. 23, 2017 Regulus Therapeutics ... discovery and development of innovative medicines targeting microRNAs, today ... 2016 financial results on Thursday, March 2, 2017 after ... conference call and webcast on March 2, 2017 at ... full year 2016 financial results and provide a general ...
(Date:2/23/2017)... The fast-growing cannabis market is expected to create ... According to the 2017 Legal Marijuana Outlook, published by New ... jobs by 2020, with an implied growth rate of more ... accelerating pace of cannabis legalization is considered as the main ... will further create more business ventures and boost the economy. ...
(Date:2/23/2017)... South Korea , Feb. 23, 2017 LG Innotek ... UV-C LED for sterilization applications. As its sterilization performance is 1.5 ... produces the short wavelength ultraviolet rays in the range of 200 -- ... the proliferation of bacteria by destroying their DNA. LG Innotek,s product ... ...
Breaking Medicine Technology: