Featured Research

from universities, journals, and other organizations

New gene sites affecting nonalcoholic fatty liver disease discovered

Date:
March 21, 2011
Source:
University of Michigan Health System
Summary:
Five genetic variants in humans -- four new -- associate with nonalcoholic fatty liver disease, according to a study.

Five genetic variants in humans -- four new -- associate with nonalcoholic fatty liver disease, according to a study published March 10 in PLoS Genetics.

NAFLD is a condition where fat accumulates in the liver (steatosis) and can lead to liver inflammation (nonalcoholic steatohepatitis or NASH) and permanent liver damage (fibrosis/cirrhosis). NAFLD affects anywhere from 11% to 45% of some populations and is associated with obesity, hypertension, and problems regulating serum lipids or glucose.

"These findings will help us to better diagnose, manage, and treat NAFLD in the future and help explain why some but not all people with obesity develop particular complications of obesity; some carry genetic variants that predispose them to some but not other metabolic diseases." says lead author Elizabeth K. Speliotes, M.D., Ph.D., M.P.H., an Assistant Professor of Gastroenterology, Internal Medicine, and Computational Medicine and Bioinformatics at the University of Michigan.

Investigators from The Old Order Amish, Age Gene-Environment Susceptibility -- Reykjavik Study , Family Heart Study, and Framingham Heart Study, collectively called the GOLD (Genetics of Obesity-related Liver Disease) Consortium meta-analyzed genome wide association data for liver steatosis from 7,126 individuals and then followed up top associating variants in cases of NASH/fibrosis from the NASH-Clinical Research Network that were genetically matched to controls from the MIGen study to find the five variants that reproducibly associate with NAFLD. All the genetic variants found increased fat deposition in the liver. However, only some affected development of inflammation/permanent damage of the liver or development of serum lipid/glucose abnormalities.

Ingrid Borecki, Ph.D., M.S., Associate Professor of Biostatistics and Genetics, co-director of the Division of Statistical Genomics at Washington University School of Medicine in Saint Louis, and senior author on the paper says "We found that approximately one quarter of the variation in NAFLD is influenced by genetic factors, and the loci we identified in the study account for about 20 percent of that genetic component. Thus the effects of these variants on NAFLD are substantial and possibly could be incorporated into clinical algorithms in the future to better classify people into risk categories. This work comes at a time when the number of people affected by these liver abnormalities is increasing, along with the prevalence of obesity in our population. Thus it is a growing problem."

Interestingly, the pattern of effects on multiple metabolic traits at two associated loci were identical and the genes closest to the best association signal at these loci are predicted to play a role in subsequent steps in triglyceride breakdown. Triglycerides are the major form of fat stored in the liver in NAFLD. This suggests that defects in triglyceride breakdown may contribute to development of NAFLD.

"Through the approaches we undertook in this study we show that we can classify genes into groups, implicating new pathways, not just genes, that affect this disease. This approach can be used to identify pathways that affect other traits as well" Speliotes says.

Speliotes notes that identifying variants and ultimately genes that affect NAFLD opens up new avenues for developing novel therapeutics for this condition. Currently, only weight loss and possibly increased physical activity can decrease hepatic steatosis. Getting people to lose weight and increase their physical activity however is a challenge worldwide, which is why obesity has become a global epidemic. This study provides possible new drug targets for therapeutic intervention of NAFLD. Further, our comprehensive examination of the effects of these genetic variants on multiple traits can help guide development of therapeutics against the gene targets of these variants so that we can chose targets that have specific effects on a desired disease while minimizing unwanted side effects.


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Journal Reference:

  1. Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Jun Wu, Ruben Hernaez, Lauren J. Kim, Cameron D. Palmer, Vilmundur Gudnason, Gudny Eiriksdottir, Melissa E. Garcia, Lenore J. Launer, Michael A. Nalls, Jeanne M. Clark, Braxton D. Mitchell, Alan R. Shuldiner, Johannah L. Butler, Marta Tomas, Udo Hoffmann, Shih-Jen Hwang, Joseph M. Massaro, Christopher J. O'Donnell, Dushyant V. Sahani, Veikko Salomaa, Eric E. Schadt, Stephen M. Schwartz, David S. Siscovick, Benjamin F. Voight, J. Jeffrey Carr, Mary F. Feitosa, Tamara B. Harris, Caroline S. Fox, Albert V. Smith, W. H. Linda Kao, Joel N. Hirschhorn, Ingrid B. Borecki. Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits. PLoS Genetics, 2011; 7 (3): e1001324 DOI: 10.1371/journal.pgen.1001324

Cite This Page:

University of Michigan Health System. "New gene sites affecting nonalcoholic fatty liver disease discovered." ScienceDaily. ScienceDaily, 21 March 2011. <www.sciencedaily.com/releases/2011/03/110310173206.htm>.
University of Michigan Health System. (2011, March 21). New gene sites affecting nonalcoholic fatty liver disease discovered. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/03/110310173206.htm
University of Michigan Health System. "New gene sites affecting nonalcoholic fatty liver disease discovered." ScienceDaily. www.sciencedaily.com/releases/2011/03/110310173206.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Fauci: Ebola Protocols to Focus on Training

Fauci: Ebola Protocols to Focus on Training

AP (Oct. 20, 2014) Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, says he expects revised CDC protocols on Ebola to focus on training, observation and ensuring health care workers are more protected. (Oct. 20) Video provided by AP
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