Featured Research

from universities, journals, and other organizations

Gene Responsible For Acetaminophen-induced Liver Injury Identified

Date:
May 11, 2009
Source:
Cold Spring Harbor Laboratory
Summary:
Acetaminophen (Tylenol and generics) is one of the most commonly used over-the-counter drugs in the United States. While generally safe, acetaminophen is known to cause severe liver injury if taken in high doses. Scientists have now found a genetic marker linked to the risk of acetaminophen-induced liver injury, using a strategy that will help develop safer drugs in the future.

Acetaminophen (Tylenol and generics) is one of the most commonly used over-the-counter drugs in the United States. While generally safe, acetaminophen is known to cause severe liver injury if taken in high doses. But likely due to genetics, even the recommended dose can induce serious liver damage in a significant number of people. Scientists have now found a genetic marker linked to the risk of acetaminophen-induced liver injury, using a strategy that will help develop safer drugs in the future.

Related Articles


Acetaminophen is considered safe over long-term use, but recent studies have indicated that even over a relatively short period, the maximum allowable dose can induce elevated levels of the liver enzyme ALT in blood serum in approximately one third of healthy individuals, suggesting possible liver injury. It is possible that if given high doses, many of these individuals would be susceptible to acute liver failure. There is likely to be a genetic predisposition, but finding the variants by scanning human subjects alone can be very difficult, requiring large studies with many participants. But with a little help from mice, researchers can overcome these experimental hurdles.

In this study, a team of researchers led by Dr. David Threadgill of North Carolina State University utilized mouse genetics to aid the search for candidate genes linked to acetaminophen-induced liver injury in humans. "We approached the study from the perspective that drugs are used in very heterogeneous patient populations, and that drug-induced toxicities are likely the result of a person's genetic makeup," Threadgill explained. The group used a genetically diverse population of mice to model human genetic variation, taking advantage of the known genetic differences in these strains to find genes linked to variable responses to acetaminophen treatment.

Once Threadgill and colleagues narrowed their search to a few candidate genes in mouse, they sequenced the genetic code of the counterparts of the same genes in human patients exhibiting elevated levels of serum ALT in response to acetaminophen. They found that a single letter change to the DNA sequence in one of these candidate genes, called CD44, is significantly associated with elevated serum ALT in these patients. While the role of this gene in liver toxicity is not yet known, CD44 could serve as a potentially useful marker to identify people at risk for acetaminophen-induced liver damage.

Threadgill noted that in addition to the identification of a gene linked to acetaminophen-induced liver injury, this study has broader implications for drug testing, as up until now, genetic differences in humans has not been considered in pre-clinical tests using animal models. "If genetic differences are included in early safety testing, more accurate predictions of clinical response will be obtained," said Threadgill. "The end result will be safer drugs."

Scientists from the University of North Carolina (Chapel Hill, NC), the Genomics Institute of the Novartis Research Foundation (San Diego, CA), the Jackson Laboratory (Bar Harbor, ME), the National Institute of Environmental Health Sciences (Research Triangle Park, NC), Verto Institute Research Laboratories (New Brunswick, NJ), the Cancer Institute of New Jersey (New Brunswick, NJ), Purdue Pharma (Stamford, CT), and North Carolina State University (Raleigh, NC) contributed to this study.

This work was supported by the National Institutes of Health and the Environmental Protection Agency.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Harrill, A.H., Watkins, P.B., Su, S., Ross, P.K., Harbourt, D.E., Stylianou, I.M., Boorman, G.A., Russo, M.W., Sackler, R.S., Harris, S.C., Contractor, T., Wiltshire, T., Rusyn, I., and Threadgill, D.W. Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res, DOI: 10.1101/gr.090241.108

Cite This Page:

Cold Spring Harbor Laboratory. "Gene Responsible For Acetaminophen-induced Liver Injury Identified." ScienceDaily. ScienceDaily, 11 May 2009. <www.sciencedaily.com/releases/2009/05/090504171943.htm>.
Cold Spring Harbor Laboratory. (2009, May 11). Gene Responsible For Acetaminophen-induced Liver Injury Identified. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2009/05/090504171943.htm
Cold Spring Harbor Laboratory. "Gene Responsible For Acetaminophen-induced Liver Injury Identified." ScienceDaily. www.sciencedaily.com/releases/2009/05/090504171943.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
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