Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immunity Gene Predicts Severe Adverse Drug Reaction

02.04.2004


In a study of Han Chinese patients, researchers have for the first time directly linked a gene of the immune system to a severe adverse drug reaction called Stevens-Johnson syndrome (SJS), according to a Duke University Medical Center medical geneticist and collaborators in Taiwan.



The sometimes fatal condition is characterized by a blistering rash that can lead to detachment of the skin and inflammation of the gastrointestinal and respiratory lining. More than 100 drugs -- including antibiotics, NSAIDS, anticonvulsants and the gout drug allopurinol -- are known to cause SJS in rare cases. The frequency with which particular prescriptions spur the devastating reaction varies among people of different ethnic backgrounds.

Their new test for the predisposing gene could be applied almost immediately to determine which of the 1.2 billion Chinese worldwide would be at risk for the reaction to the popular anti-epilepsy drug carbamazepine (trade name Tegretol), said Y-T Chen, M.D., chief of medical genetics at Duke University Medical Center and director of the Institute of Biomedical Sciences at Academia Sinica in Taiwan. The anticonvulsant is the most common cause of SJS among the Chinese population.


The finding highlights the promise of pharmacogenomics for avoiding drugs’ most serious side effects and might also lead to advances in the clinical trial of new drugs, said the researchers.

A single genetic marker predicted with 100 percent accuracy those who could safely take carbamazepine, the team reported in the April 1, 2004, issue of Nature. Individuals with a particular version of the immunity gene who took the drug suffered the devastating reaction in all but 3 percent of the cases.

Whether the gene variant will predict the drug reaction in people of other ethnic backgrounds remains to be tested, said Chen. However, his team expects that other similar genes will be found to underlie the reaction induced by the many other drugs that have been linked to SJS. Such findings would enable drug-specific genetic screening tests to prevent the condition.

"In the near future, physicians will be able to test patients’ genetic makeup before prescribing medications in order to predict those that are likely to have a severe adverse reaction," Chen said. "The technology is here and there will be more advances to come."

Understanding such genetic interactions might also prove a boon to new drug development, said Chen, noting that some drugs have been eliminated in the clinical trial phase because they produced SJS symptoms in some participants.

In the United States, the condition, which is fatal in 10 percent of cases, occurs in approximately 500 people per year. The condition is four or five times more common in the Chinese population in comparison to the U.S., said Chen. Many more people worldwide are at risk of SJS should they take particular prescription drugs, he added.

Adverse drug reactions stem from two primary causes. In some cases, drug concentrations build to toxic levels due to a person’s genetic inability to metabolize the medication. In others, elements of the immune system mobilize and attack the drug, thereby producing the symptoms.

The investigators screened genetic factors known to play a role in drug metabolism and the immune response in three groups:

-- 44 patients with carbamazepine-induced SJS
-- 101 patients that had taken the drug for three months with no adverse reaction
-- 93 healthy individuals not taking the drug.

All patients with SJS carried the genetic variant human leukocyte antigen B* 1502 (HLA-B* 1502), while only 3 percent of those tolerant of the drug carried that version of the HLA gene, the team found.

HLA markers -- perhaps most familiar for their use in determining suitable matches for bone marrow transplantation -- play a critical role in the immune system’s recognition of foreign invaders, whether infectious agents or foreign substances such as medications, explained Chen.

The team has set out to identify other genetic markers linked to severe adverse reactions to other drugs. They also plan to further examine the precise mechanism underlying the connection between HLA-B* 1502 and carbamazepine-induced SJS.

Collaborators include Wen-Hung Chung, M.D., Hong-Shang Hong, M.D., Hsin-Chun Ho, M.D., Mo-Song Hsih, M.D., and Li-Cheng Yang, M.D., all of Chang Gung Memorial Hospital in Taiwan; Jer-Yuarn Wu, Ph.D.; and Shuen-Iu Hung, Ph.D., of Academia Sinica.

Kendall Morgan | dukemed news
Further information:
http://www.dukemednews.org/news/article.php?id=7501

More articles from Studies and Analyses:

nachricht Robocabs: The mobility of the future?
25.06.2019 | Fraunhofer-Institut für Arbeitswirtschaft und Organisation IAO

nachricht Self-organising system enables motile cells to form complex search pattern
07.05.2019 | Westfälische Wilhelms-Universität Münster

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Cooling with the sun

25.06.2019 | Power and Electrical Engineering

Robocabs: The mobility of the future?

25.06.2019 | Studies and Analyses

Skipping Meat on Occasion May Protect Against Type 2 Diabetes

25.06.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>