Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic mutation found that is major contributor to type 1 diabetes

12.07.2004


A natural mutation of a gene that helps regulate the reactivity of the immune system is a major contributor to type 1 diabetes, Medical College of Georgia researchers have found.



The newly discovered gene, SUMO-4, controls the activity of NFêB, a molecule that in turn controls the activity of cytokines, proteins that regulate the intensity and duration of the immune response, according to research that will be published in the August print issue of Nature Genetics and online July 11.

By examining the transmission of genes from parents to children in nearly 1,000 diabetic families from around the world, the researchers found that a certain natural mutation of that SUMO-4 gene increases the risk of type 1 diabetes.


"This helps us understand how type 1 diabetes works, and we can use this improved understanding to better predict who will get the disease and design new intervention strategies for those who do," said Dr. Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine and a co-senior author on the study.

"The mutation we have found is going to increase the responsive capacity of the immune system to environmental triggers or stimulators; it makes it more reactive," said Dr. Cong-Yi Wang, molecular geneticist and co-senior author.

Dr. Wang and his research team found that when that mutation encounters an environmental trigger, such as a bacterial or viral infection, it throws off the usual well-balanced activity of the immune system, initiating an autoimmune response that eventually attacks the patient’s own tissue.

They already are exploring the gene’s potential role in other autoimmune diseases as well such as lupus, thyroid disease, arthritis and multiple sclerosis.

SUMO-4 is the fourth gene identified that contributes to type 1 diabetes, taking a place just behind HLA, another regulator of immunity, in terms of relative risk. "Many genes are involved in type 1 diabetes, but this is one of the most important ones," said Dr. She. He leads a research team that has followed diabetic families primarily in Florida and Georgia for the past 10 years to find precisely how genes, the immune system and the environment work together to cause type 1 diabetes, a childhood disease that requires a lifetime of taking insulin. Like its lifestyle-related counterpart, type 2 diabetes, the incidence of type 1 has increased dramatically: a near 300 percent increase in the last 20 years.

This is one of the few times scientists have successfully used a systematic approach to finding a gene involved in a complex disease such as diabetes. The MCG researchers narrowed their search for diabetes-related genes by looking at those most often transmitted to children with diabetes, Dr. She said. That approach compares with traditional forward genetics — a cumbersome process they liken to looking for a needle in a haystack — which narrows the search by predicting which of some 40,000 genes might be involved in a disease based on what scientists already know about the disease and the genes.

"You guess the function, you guess the disease possibilities, then you guess which genes might be involved in the pathogenesis," Dr. She said. "As a community, we have guessed right a few times, including identification of HLA. But this is the first time we have used a systematic approach to find the gene and it’s the first gene in which we know how it contributes to the disease."

For example, HLA is a regulator of immunity that has been known for 30 years, but researchers still don’t know exactly how it causes diabetes. The MCG team has found that SUMO-4 encodes a protein that modifies the activity of NFêB. It was already known that NFêB regulates the production of certain cytokines and that cytokines have a role in type 1 diabetes as well as other autoimmune diseases. What wasn’t known was the cause of the excessive cytokine production seen in those diseases. Now they know that SUMO-4 regulates the activity of NFêB, which in turn regulates whether cytokine production is on autopilot, shut down or revved up.

The SUMO-4 mutation they found overrides the systems that put cytokine production on autopilot or shut it down. Instead, it enables cytokine production not only to increase but directs the increased immune response at the insulin-producing beta cells of the pancreas.

Dr. She credits many for the findings but especially Dr. Wang for his diligence in working through this more systematic — but still extremely tedious — approach to identifying not only the gene but how it causes disease.

"This is the reason scientists stay in science," Dr. She said. "These are the days you look for, days when you can make a difference, not just for science, but for humanity, for patients, for people who have diabetes and, perhaps even more, for people who are going to develop diabetes." He noted that none of the work would be possible without the contributions of study families. "We are trying to improve their lives, but without them, we cannot do anything."

The studies were funded by National Institute of Child Health and Development and the Juvenile Diabetes Research Foundation. Collaborators included researchers at the University of Florida; Endocrinologia, Instituto Clinica Medica II, University of Rome; the University of Southern California School of Medicine, Los Angeles; Cedars-Sinai Medical Center and the University of California, Los Angeles; Hanyang University Hospital in Korea; Facultad de Medicina, Universidad Complutense in Madrid; HLA Laboratory, Beijing Red Cross Blood Center, China; and Unite de Recherches de 1’INSERM U580, Centre de l’Association Claude Bernard, France.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>