Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genes may exert opposite effects in diabetes and inflammatory bowel disease

23.03.2010
Both autoimmune diseases may respond to a 2-way genetic switch

Pediatric researchers analyzing DNA variations in type 1 diabetes and inflammatory bowel disease have found a complex interplay of genes. Some genes have opposing effects, raising the risk of one disease while protecting against the other. In other cases, a gene variant may act in the same direction, raising the risk for both diseases.

Both type 1 diabetes (T1D) and inflammatory bowel disease (IBD) are autoimmune disorders—conditions in which the body's immune system overreacts, resulting in disease. Many such autoimmune diseases share genes in common, acting on shared biological pathways.

"This finding shows the genetic architecture of these diseases is more complex than previously thought," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "We knew that multiple genes that interact with each other and with environmental factors are needed to bring on these complex diseases, and we are still detecting these genes and uncovering those interactions. But we now see that some genes influence more than one disease, and sometimes in the opposite direction."

Hakonarson and colleagues, including collaborators from more than a dozen institutions in four countries, published the study online in an advance article on Feb. 22 in Human Molecular Genetics.

Inflammatory bowel disease consists of Crohn's disease (CD), which may affect the entire digestive tract, but especially the small intestine, and ulcerative colitis (UC), mainly affecting the large intestine. Type 1 diabetes, also called insulin-dependent diabetes, occurs when the body produces little or no insulin because the immune system destroys insulin-producing cells.

The study team analyzed samples from 1,689 children and adolescents with CD, 777 with UC, and 989 with type 1 diabetes, as well as 6,197 control samples from healthy children. All the children were of European ancestry. The IBD and T1D samples were all from patients with early-onset disease, i.e., occurring by age 19.

The genome-wide association study (GWAS) identified multiple gene variants not previously reported for these diseases, in addition to evaluating genes previously discovered to be associated with one, two or all three diseases. The study team found overlaps among gene variants that conferred risk for both T1D and IBD. They also found four variants impacting the genes PTPN22, IL27, IL18RAP and IL10 that raised the risk of T1D while lowering the risk of Crohn's disease.

These opposing effects, said Hakonarson, could suggest a possible "genetic switch" on some biological pathways involved in both IBD and type 1 diabetes. "For these autoimmune disorders, the switch could be activated by specific infectious agents that trigger immune responses that are mediated by selective immunological pathways," he said. He noted that a pathogen could interact with a gene that raises the risk for type 1 diabetes at the same time it confers protection from Crohn's disease. "Infections cause a lot of adaptation within the immune system, and could be exerting selective pressure in driving genomes to evolve, where the resulting disease risk or protection is more of a bystander," Hakonarson added.

Hakonarson cautioned that the potential genetic switch is currently an interesting hypothesis, requiring further investigation. Even the four gene variants (single nucleotide polymorphisms, or SNPs) that seem to cause opposing effects for these diseases may be markers for yet unknown causative genes that act in the same direction. "We won't know the exact impact of these variants until we have more sequencing data," he concluded.

Funding for this study came from The Children's Hospital of Philadelphia, through an Institute Development Award to the Center for Applied Genomics; from Genome Canada through the Ontario Genomics Institute and the Juvenile Diabetes Research Foundation; the Primary Children's Medical Center Foundation; and the National Center for Research Resources of the National Institutes of Health.

"Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects," Human Molecular Genetics, advance access published Feb. 22, 2010. doi:10.1093/hmg/ddq078

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 443-bed hospital recognition as a leading advocate for children and adolescents.

John Ascenzi | EurekAlert!
Further information:
http://www.chop.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>