These authors contributed equally to this work.
Steatohepatitis/Metabolic Liver Disease
Article first published online: 7 DEC 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 53, Issue 1, pages 86–95, January 2011
How to Cite
Stickel, F., Buch, S., Lau, K., zu Schwabedissen, H. M., Berg, T., Ridinger, M., Rietschel, M., Schafmayer, C., Braun, F., Hinrichsen, H., Günther, R., Arlt, A., Seeger, M., Müller, S., Seitz, H. K., Soyka, M., Lerch, M., Lammert, F., Sarrazin, C., Kubitz, R., Häussinger, D., Hellerbrand, C., Bröring, D., Schreiber, S., Kiefer, F., Spanagel, R., Mann, K., Datz, C., Krawczak, M., Wodarz, N., Völzke, H. and Hampe, J. (2011), Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians. Hepatology, 53: 86–95. doi: 10.1002/hep.24017
Supported by the German National Genome Research Network (NGFN) through the POPGEN biobank (BmBF 01GR0468) and NGFN plus (BmBF 01GS08152) and the BmBF systems biology networks QuantLiver (BmBF 0313853D) and Virtual Liver. The Community Medicine Research net (CMR) of the University of Greifswald is funded by the Federal Ministry of Education and Research, the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. The CMR encompasses several research projects sharing data from the population-based Study of Health in Pomerania.
Potential conflict of interest: Nothing to report.
- Issue published online: 12 JAN 2011
- Article first published online: 7 DEC 2010
- Accepted manuscript online: 30 SEP 2010 09:16AM EST
- Manuscript Accepted: 18 SEP 2010
- Manuscript Received: 19 MAR 2010
Vol. 53, Issue 4, 1415, Article first published online: 11 MAR 2011
A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; Pgenotype = 1.2 × 10−5; Pallelic = 1.6 × 10−6) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; Pgenotype = 0.0085; Pallelic = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; Pgenotype = 0.040; Pallelic = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (Pcombined = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. Conclusion: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians. (HEPATOLOGY 2011)