Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Genetic Mystery of Behcet's Disease Unfolds Along the Ancient Silk Road

Published: Monday, January 07, 2013
Last Updated: Monday, January 07, 2013
Bookmark and Share
NIH researchers identify new gene variants associated with risk for complex inflammatory syndrome.

Researchers have identified four new regions on the human genome associated with Behcet's disease, a painful and potentially dangerous condition found predominantly in people with ancestors along the Silk Road. For nearly 2,000 years, traders used this 4,000-mile network linking the Far East with Europe to exchange goods, culture and, in the case of the Silk Road disease, genes. National Institutes of Health researchers and their Turkish and Japanese collaborators published their findings in the Jan. 6, 2013, advance online issue of Nature Genetics.

Named for the Turkish physician who described it in 1937, Behcet’s (pronounced BET’-chets) disease is triggered by complex genetic and environmental factors, and causes inflammation of blood vessels in various parts of the body. Common symptoms include painful mouth and genital sores, and eye inflammation that can lead to blindness. In some cases, it can be life-threatening, affecting blood vessels in the brain, lungs, and other vital organs. About 1 in 250 people in Turkey have Behcet's disease; others with the disease are found largely in regions along the Silk Road.

Genetic factors are thought to play a role in susceptibility to Behcet's disease, with the human leukocyte antigen (HLA) B-51 gene region of the genome, accounting for about 20 percent of genetic risk for the disease. Researchers have been aware of the HLA B-51 association for about 40 years. Two years ago, the research team identified gene associations at two other specific chromosome locations, or loci.

"The current study represents an important advance because it dramatically broadens the spectrum of genetic loci associated with Behcet's disease," said Dan Kastner, M.D., Ph.D., scientific director of the Intramural Research Program at the National Human Genome Research Institute and senior author of the study. "These newly discovered genetic associations provide a link between Behcet’s disease and other more common illnesses, and thereby suggest new therapies for Behcet’s disease. In addition, two of the newly discovered genes provide an intriguing link between genes and the microbes in our environment."

Researchers conducted a genome-wide association study (GWAS) that enrolled 1,209 Turkish people affected by Behcet's disease and 1,278 unaffected Turkish people — all residents of the country. They looked at many points on the human genome called single-nucleotide polymorphisms (SNPs), with each SNP representing a difference in a single DNA building block, called a nucleotide. Researchers then compared SNP differences between people with and without disease.

From nearly 800,000 SNPs, researchers detected and mapped a small number that are found in those who have Behcet’s disease at a significantly higher rate than in those without the disease, suggesting that the variant or another one nearby contributes to the disease.

"Each of the genetic factors may contribute a little to the overall risk of disease," said Elaine F. Remmers, Ph.D., staff scientist in NHGRI’s Inflammatory Disease Section and study co-author. "We are also identifying them in pathways that are important in inflammatory disease development."

She noted that not all of the 800,000 gene variants analyzed were directly genotyped. Genotyping involves examining a person's DNA at a site where a variation is commonly known to occur. Instead, the team used the strategy of imputing, or surmising, that there were genotypes worth investigating near known variants.

"That worked very well for us," Dr. Remmers said. "We found that our predicted genotypes were pretty good and that the associations we found were quite similar in both the predicted and the experimentally confirmed genotypes."

Each of the four newly identified gene regions is already known to play a role in immune regulation. The genetic associations have helped classify Behcet’s disease with more common inflammatory conditions such as psoriasis, inflammatory bowel disease and a form of spinal arthritis called ankylosing spondylitis.

Among the newly identified regions, researchers found:

•    An important association between Behcet’s disease and a gene called ERAP1. ERAP1 codes for a molecule that processes microbial proteins in white blood cells. Variants of this protein can lead to more or less efficient processing of microbial proteins before they are loaded onto HLA molecules for presentation to the immune system. The variants of ERAP1 identified in this study increase the risk of Behcet's disease, but only in those individuals with one specific HLA type, HLA-B51, which has previously been associated with Behcet’s disease. Dr. Kastner speculates that the ERAP1 variant associated with Behcet’s disease processes microbial proteins in such a way that they can be loaded onto the HLA-B51 molecule to trigger an abnormal immune response. The very same variant of ERAP1 that is associated with Behcet's disease is protective for ankylosing spondylitis and psoriasis, but only in people with the HLA types associated with those diseases.
•    A significant association of Behcet's disease with variants near the CCR1 gene. Proteins coded by this gene help infection-fighting blood cells migrate to sites of invading microorganisms. When this function is defective, the microorganisms can trigger a persistent inflammatory response.
•    An association of the disease with variants in the KLRC4 gene. The function of the receptor protein coded by this gene is not well understood, but the researchers suggest that it may be important to investigate further because it is located within the genomic region with the strongest evidence for linkage to a disease gene in a study of Turkish family health histories in which members sometimes have a rare familial form of Behcet’s disease.
•    An association with the STAT4 gene, in which different variants in the same vicinity of the genome increase risk for autoimmune diseases, including rheumatoid arthritis and lupus.

"We are incredibly excited about these latest findings," Dr. Kastner said. "Combined with our studies two years ago, the current genetic data make a strong case for a causal connection between Behcet’s disease and disorders such as ankylosing spondylitis, psoriasis, and inflammatory bowel disease. This raises real hope that some of the treatments that have been found effective in these other illnesses will have some utility in Behcet’s disease, thereby helping to alleviate suffering and prevent mortality."


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

NIH Grants Seek Best Ways To Combine Genomic Information and EHRs
Researchers seek to better understand genomic basis of disease, provide tailored care to patients.
Friday, September 04, 2015
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Wednesday, September 02, 2015
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Tuesday, September 01, 2015
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Thursday, August 27, 2015
NIH Launches Human RSV Study
Study aims to understand infection in healthy adults to aid development of RSV medicines, vaccines.
Thursday, August 27, 2015
In Uveitis, Bacteria in Gut May Instruct Immune Cells to Attack the Eye
NIH scientists propose novel mechanism to explain autoimmune uveitis.
Wednesday, August 19, 2015
Novel Mechanism to Explain Autoimmune Uveitis Proposed
A new study on mice suggests that bacteria in the gut may provide a kind of training ground for immune cells to attack the eye.
Wednesday, August 19, 2015
Large Percentage of Youth with HIV May Lack Immunity to Measles, Mumps, Rubella
NIH study finds those vaccinated before starting modern HIV therapy may be at risk.
Tuesday, August 18, 2015
Cellular Factors that Shape the 3D Landscape of the Genome Identified
Researchers have identified 50 cellular factors required for the proper 3D positioning of genes by using novel large-scale imaging technology.
Tuesday, August 18, 2015
Nuclear Process in the Brain That May Affect Disease Uncovered
Scientists have shown that the passage of molecules through the nucleus of a star-shaped brain cell, called an astrocyte, may play a critical role in health and disease.
Tuesday, August 18, 2015
Scientists Uncover Nuclear Process in the Brain that May Affect Disease
NIH-funded study highlights the possible role of glial brain cells in neurological disorders.
Tuesday, August 18, 2015
Newly Discovered Cells Restore Liver Damage in Mice Without Cancer Risk
The liver is unique among organs in its ability to regenerate after being damaged. Exactly how it repairs itself remained a mystery until recently, when researchers supported by the NIH discovered a type of cell in mice essential to the process
Monday, August 17, 2015
Study Finds Cutting Dietary Fat Reduces Body Fat More than Cutting Carbs
In a recent study, restricting dietary fat led to body fat loss at a rate 68 percent higher than cutting the same number of carbohydrate calories when adults with obesity ate strictly controlled diets.
Friday, August 14, 2015
Inappropriate Medical Food Use in Managing Patients with a Type of Metabolic Disorder
Researchers have proposed that there is a need for more rigorous clinical study of dietary management practices for patients with IEMs, including any associated long-term side effects, which may in turn result in the need to reformulate some medical foods.
Friday, August 14, 2015
PINK1 Protein Crucial for Removing Broken-Down Energy Reactors
NIH study suggests potential new pathway to target for treating ALS and other diseases.
Thursday, August 13, 2015
Scientific News
Health Risks of Saturated Fats Aggravated by Immune Response
Research shows that the presence of saturated fats resulted in monocytes migrating into the tissues of vital organs.
Changing the Biological Data Visualisation World
Scientists at TGAC, alongside European partners, have created a cutting-edge, open source community for the life sciences.
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!