Featured Research

from universities, journals, and other organizations

Genetic variants linked to severe skin reactions to antiepileptic drug identified

Date:
August 5, 2014
Source:
JAMA - Journal of the American Medical Association
Summary:
Researchers have identified genetic variants that are associated with severe adverse skin reactions to the antiepileptic drug phenytoin, according to a new study. Phenytoin is a widely prescribed antiepileptic drug and remains the most frequently used first-line antiepileptic drug in hospitalized patients.

Researchers have identified genetic variants that are associated with severe adverse skin reactions to the antiepileptic drug phenytoin, according to a study in the August 6 issue of JAMA.

Related Articles


Phenytoin is a widely prescribed antiepileptic drug and remains the most frequently used first-line antiepileptic drug in hospitalized patients. Although effective for treating neurological diseases, phenytoin can cause cutaneous (skin) adverse reactions ranging from mild to severe. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions has not been known, according to background information in the article.

Wen-Hung Chung, M.D., Ph.D., of Chang Gung Memorial Hospital, Keelung, Taiwan, and colleagues investigated the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The case-control study was conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema (a less severe type of rash), 130 phenytoin-tolerant control participants, and 3,655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS) was conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan.

Analysis of the data indicated that variants of the gene CYP2C, including CYP2C9*3, were associated with phenytoin-related severe cutaneous adverse reactions. The statistically significant association between CYP2C9*3, known to reduce drug clearance (the elimination of a drug from the body), and phenytoin-related severe cutaneous adverse reactions was replicated by the samples from Taiwan, Japan, and Malaysia, with a meta-analysis showing an 11 times higher odds of experiencing this reaction with this variant. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a clinical link of the associated variants to the disease.

Delayed clearance was also noted in patients with severe cutaneous adverse reactions without CYP2C9*3, suggesting that nongenetic factors such as renal insufficiency, hepatic dysfunction, and concurrent use of substances that compete or inhibit the enzymes may also affect phenytoin metabolism and contribute to severe cutaneous adverse reactions.

"This study identified CYP2C variants, including CYP2C9*3, known to reduce drug clearance, as important genetic factors associated with phenytoin-related severe cutaneous adverse reactions. These findings may have potential to improve the safety profile of phenytoin in clinical practice and offer the possibility of prospective testing for preventing phenytoin-related severe cutaneous adverse reactions. More research is required to replicate the genetic association in different populations and to determine the test characteristics and clinical utility," the authors conclude.


Story Source:

The above story is based on materials provided by JAMA - Journal of the American Medical Association. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wen-Hung Chung, Wan-Chun Chang, Yun-Shien Lee, Ying-Ying Wu, Chih-Hsun Yang, Hsin-Chun Ho, Ming-Jing Chen, Jing-Yi Lin, Rosaline Chung-Yee Hui, Ji-Chen Ho, Wei-Ming Wu, Ting-Jui Chen, Tony Wu, Yih-Ru Wu, Mo-Song Hsih, Po-Hsun Tu, Chen-Nen Chang, Chien-Ning Hsu, Tsu-Lan Wu, Siew-Eng Choon, Chao-Kai Hsu, Der-Yuan Chen, Chin-San Liu, Ching-Yuang Lin, Nahoko Kaniwa, Yoshiro Saito, Yukitoshi Takahashi, Ryosuke Nakamura, Hiroaki Azukizawa, Yongyong Shi, Tzu-Hao Wang, Shiow-Shuh Chuang, Shih-Feng Tsai, Chee-Jen Chang, Yu-Sun Chang, Shuen-Iu Hung. Genetic Variants Associated With Phenytoin-Related Severe Cutaneous Adverse Reactions. JAMA, 2014; 312 (5): 525 DOI: 10.1001/jama.2014.7859

Cite This Page:

JAMA - Journal of the American Medical Association. "Genetic variants linked to severe skin reactions to antiepileptic drug identified." ScienceDaily. ScienceDaily, 5 August 2014. <www.sciencedaily.com/releases/2014/08/140805163254.htm>.
JAMA - Journal of the American Medical Association. (2014, August 5). Genetic variants linked to severe skin reactions to antiepileptic drug identified. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2014/08/140805163254.htm
JAMA - Journal of the American Medical Association. "Genetic variants linked to severe skin reactions to antiepileptic drug identified." ScienceDaily. www.sciencedaily.com/releases/2014/08/140805163254.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
Ebola: Life Without School in Guinea

Ebola: Life Without School in Guinea

AFP (Nov. 21, 2014) Following the closure of schools and universities in Guinea because of the Ebola virus, students look for temporary work or gather in makeshift classrooms to catch up on their syllabus. Duration: 02:14 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins