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

Dec 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 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 to obvious cirrhosis," Dr. Hampe concluded. "Carriers of this risk allele should be targeted for future pharmaceutical treatments and non-pharmacological interventions."

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More information: "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.

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User comments : 2

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gwrede
5 / 5 (1) Dec 16, 2010
I rated this article 5 stars, even when I'm not interested in alcohol research or biochemistry. Why?

This article is well formed. The ingress summarises the article well, and manages to do most of it right at the start, so that a mouse-over pops up the relevant info.

The article exposes background and objective, and only then mentions authors. Then follows what was done and how, what was found, and finally the conclusions and suggestions.

The very end is then for background information, such as enumerating the participants, and nice-to-know things.

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One would hope that this structure would be obligatory for all articles here. Just as an example, here's what you see of another article:
In a truly interdisciplinary effort, a team of biomedical scientists and engineers from the University of Houston (UH) and physicians from The Methodist Hospital Research Institute (TMHRI) are collaborating ...
That's all you see. It helps nobody.
Modernmystic
not rated yet Dec 16, 2010
How about: Alcholohics beware--if you keep drinking you're going to lose your job, your house, your family, you run a good chance of killing someone driving and going to jail, oh and you'll probably kill yourself either intentionally or in a drunken stupor within 10 years....

Oh and your liver is probably the LEAST of your worries, especially if you're in the midst of your addiction.

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