Genetic Variation Associated with Alcoholic Liver Disease

Genotyping has revealed that gene variation is strongly linked with cirrhosis of the liver and elevated transaminase levels in alcoholic Caucasians.

Blood tests for liver enzymes and genotyping of patients' DNA pinpoint the risk and susceptibility to progress towards alcoholic liver disease in those who drink excessive amounts of alcohol, which may be fatal.

Scientists from the University of Bern (Bern, Switzerland) and the Christian-Albrechts-University (Kiel, Germany) determined the genotype and allele frequencies of the adiponutrin or patatin-like phospholipase (PNPLA3) gene. Adiponutrin a transmembrane protein specifically expressed in adipose tissue. Participants in the study included 1,043 alcoholics with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort.

Cirrhosis and steatosis (fatty liver) were determined by liver biopsy and standard diagnostic testing. The liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of the participants 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.

The results of the study showed that single nucleotide polymorphism (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. The gene was associated with cirrhosis of the liver and elevated transaminase levels in alcoholic Caucasians.

Jochen Hampe, MD, the lead author, concluded that carriers with the genetic variation, PNPLA3 rs738409, represent a subpopulation of high-risk individuals susceptible to progression from clinically silent alcoholic liver disease to obvious cirrhosis. The study was published online December 7, 2010, in Hepatology.

Related Links:
University of Bern
Christian-Albrechts-University