Alcoholics beware -- genetic variation linked to liver cirrhosis in Caucasians

December 16, 2010

A new study by German researchers found that a variation in the PNPLA3 (adiponutrin) gene was associated with cirrhosis of the liver and elevated transaminase (liver enzyme) levels in alcoholic Caucasians. The risk of cirrhosis in alcoholics in the genetic high risk group might be as high as 25% to 50%. Full findings are published in the January 2011 issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.

Alcoholic liver disease (ALD)--ranging from alcoholic fatty liver to alcohol induced liver fibrosis and cirrhosis--accounts for more than 50% all chronic liver disease in industrialized countries and was responsible for over 25,000 deaths in the U.S. alone in 2005. Studies have shown that while all heavy drinkers display signs of hepatitis steatosis (fatty liver), only 10% to 35% of alcoholics develop hepatic inflammation, with up to 20% progressing to cirrhosis. Further medical evidence suggests a link between PNPLA3 gene variation and liver fat content; specifically the single nucleotide polymorphism (SNP) rs738409 was reported previously to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of European and Native American descent.

The German research team led by Jochen Hampe, MD, from Christian-Albrechts-Universität Kiel determined the genotype and allele frequencies of PNPLA3 rs738409 in 1043 alcoholics with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Cirrhosis and steatosis was determined by liver biopsy and standard diagnostic testing. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were established using routine clinical chemistry testing.

Participants were categorized as alcoholic liver cirrhosis (ALC); alcoholics with liver steatosis on ultrasound and elevation of ALT as alcoholic liver damage (ALD); alcoholic liver steatosis and normal liver enzyme levels as alcoholic fatty liver (AFL); and alcoholics with normal appearance of the liver on ultrasound and normal liver enzyme levels as alcoholic controls.

Researchers discovered that SNP rs738409 was strongly over-represented in patients with ALC and ALD compared to alcoholics without liver damage. Additionally, the frequency of allele PNPLA3 rs738409 in AFL participants was lower than in alcoholics without steatosis and normal liver enzymes. "Our findings show PNPLA3 rs738409 carriers represent a subpopulation of high risk individuals susceptible to progression from clinically silent alcoholic liver disease to obvious cirrhosis," Dr. Hampe concluded. "Carriers of this risk allele should be targeted for future pharmaceutical treatments and non-pharmacological interventions."
-end-
Article: "Genetic Variation in the PNPLA3 Gene is Associated with Alcoholic Liver Injury in Caucasians." Felix Stickel, Stephan Buch, Katharina Lau, Henriette Meyer zu Schwabedissen, Thomas Berg, Monika Ridinger, Marcella Rietschel, Clemens Schafmayer, Felix Braun, Holger Hinrichsen, Rainer Günther, Alexander Arlt, Marcus Seeger, Sebastian Müller, Helmut Karl Seitz, Michael Soyka, Markus Lerch, Frank Lammert, Christoph Sarrazin, Ralf Kubitz, Dieter Häussinger, Claus Hellerbrand, Dieter Bröring, Stefan Schreiber, Falk Kiefer, Rainer Spanagel, Karl Mann, Christian Datz, Michael Krawczak, Norbert Wodarz, Henry Völzke, Jochen Hampe. Hepatology; Published Online: December 7, 2010 (DOI: 10.1002/hep.24017); Print Issue Date: January 2011. http://onlinelibrary.wiley.com/doi/10.1002/hep.24017/abstract.

This study is published in Hepatology. Media wishing to receive a PDF of this article may contact healthnews@wiley.com.

About the Journal

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1527-3350 .

About Wiley-Blackwell

Wiley-Blackwell is the international scientific, technical, medical, and scholarly publishing business of John Wiley & Sons, with strengths in every major academic and professional field and partnerships with many of the world's leading societies. Wiley-Blackwell publishes nearly 1,500 peer-reviewed journals and 1,500+ new books annually in print and online, as well as databases, major reference works and laboratory protocols. For more information, please visit www.wileyblackwell.com or our new online platform, Wiley Online Library (wileyonlinelibrary.com), one of the world's most extensive multidisciplinary collections of online resources, covering life, health, social and physical sciences, and humanities.

Wiley

Related Cirrhosis Articles from Brightsurf:

Researchers discover gene that could decrease likelihood of developing alcoholic cirrhosis
Researchers at Indiana University School of Medicine are learning more about how a person's genes play a role in the possibility they'll suffer from alcoholic cirrhosis with the discovery of a gene that could make the disease less likely.

When liver cirrhosis is deadly
A study by an international team of researchers headed by Professor Jonel Trebicka from the Frankfurt University Hospital and funded by the foundation EF Clif, has discovered which patients are particularly at risk for acute-on-chronic liver failure.

Blood tests can predict the risk of liver cirrhosis
Repeated measurements of the biomarker FIB-4 in the blood every few years can predict the risk of developing severe liver disease, according to a new study from Karolinska Institutet in Sweden published in the Journal of Hepatology.

Universal gut microbiome-derived signature predicts cirrhosis
UC San Diego School of Medicine researchers report that stool microbiomes of NAFLD patients are distinct enough to potentially be used to accurately predict which persons with NAFLD are at greatest risk for having cirrhosis.

Strength training benefits patients with cirrhosis
Three hours of weekly strength training combined with protein supplements leads to both bigger and stronger muscles in patients with cirrhosis.

Women are not more likely to die of cirrhosis than men, despite fewer liver transplants
Prior studies suggested women might have higher mortality of cirrhosis of the liver than men.

Movement toward a poop test for liver cirrhosis
In a study of people with nonalcoholic fatty liver disease and their twins and other close relatives, UC San Diego researchers were able to diagnose liver cirrhosis simply by analyzing a person's stool microbes.

Gum disease treatment may improve symptoms in cirrhosis patients
Routine oral care to treat gum disease (periodontitis) may play a role in reducing inflammation and toxins in the blood (endotoxemia) and improving cognitive function in people with liver cirrhosis.

Alcohol-related cirrhosis deaths skyrocket in young adults
Liver disease deaths jumped by 65 percent in the United States, from 1999-2016, disproportionately affecting adults ages 25-34.

Researchers find a promising new approach for treating liver cirrhosis
In a study in The American Journal of Pathology, investigators report that treatment with aleglitazar, a dual peroxisome proliferator-activated receptor-alpha/gamma (PPARα/γ) agonist, reduced inflammation, vasoconstriction, angiogenesis, mucosal disruption, and tumor necrosis factor (TNF)-α overproduction in cirrhotic rats with PH.

Read More: Cirrhosis News and Cirrhosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.