Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

• DOI: 10.1002/hep.24017
• Publication Date: 2010-09-30T14:17:37Z
• Authors: Felix Stickel; Stephan Buch; Katharina Lau; Henriette Meyer z...; 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
• Keywords: Variation (astronomy)

A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic disease alcohol-dependent individuals of Mestizo descent. We therefore evaluated impact on manifestation two independent German cohorts. Genotype allele frequencies were determined 1,043 patients or without injury 376 at-risk drinkers from a population-based cohort. Relative damage (n = 439), genotype GG strongly overrepresented cirrhosis 210; OR 2.79; P(genotype) 1.2 × 10(-5) ; P(allelic) 1.6 10(-6) ) but elevated alanine aminotransferase levels 219; 2.33; 0.0085; 0.0042). The latter, biochemically defined confirmed cohort median alcohol intake 300 g/week (OR 4.75; 0.040; 0.022), for aspartate (AST) levels. Frequencies rs738409(G) steatosis normal (ALT) AST lower than alcoholics ALT/AST (P(combined) 0.03). population attributable risk carriers estimated at 26.6%. rs738409(GG) is Caucasians.