BACKGROUND: Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin-like phospholipase domain-containing 3 gene (PNPLA3). AIM: To evaluate the influence of this variant on ALC and other forms of ALD. METHODS: We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis was conducted in a random-effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed. RESULTS: Database search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25-5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67-2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALD patients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD. CONCLUSION: Our meta-analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.
BACKGROUND: Several studies have reported an association between alcoholic liver cirrhosis (ALC) or other forms of alcoholic liver disease (ALD) and the genetic variant rs738409 (C>G) in adiponutrin/patatin-like phospholipase domain-containing 3 gene (PNPLA3). AIM: To evaluate the influence of this variant on ALC and other forms of ALD. METHODS: We performed a systematic review of previous studies on the relationship between rs738409 of PNPLA3 and ALD and meta-analysis was conducted in a random-effects model. Calculations of the odds ratios (ORs) and their confidence intervals (CIs), tests for heterogeneity and sensitivity analyses were performed. RESULTS: Database search identified 11 previous studies available for inclusion with a total of 3495 patients with ALD (2087 with ALC) and 5038 controls (4007 healthy subjects and 1031 alcoholics without ALD). Patients with ALC compared to controls had a significantly higher prevalence of the G allele when comparing GG vs. CC (OR 4.30, 95% CI 3.25-5.69; P < 0.00001) or GC vs. CC genotypes (GC vs. CC: OR 1.91, 95% CI 1.67-2.17) or under a recessive or dominant model. Similar results were found when comparing separately patients with ALC vs. alcoholics without ALD or healthy subjects. An association of the G allele with ALD emerged when comparing ALDpatients vs. alcoholics without ALD and/or healthy subjects although moderate to large heterogeneity was observed. Our data suggested an additive genetic model for this variant in ALD. CONCLUSION: Our meta-analysis shows that the rs738409 variant of PNPLA3 is clearly associated with alcoholic liver cirrhosis.
Authors: Sathish Kumar Natarajan; Karuna Rasineni; Murali Ganesan; Dan Feng; Benita L McVicker; Mark A McNiven; Natalia A Osna; Justin L Mott; Carol A Casey; Kusum K Kharbanda Journal: Curr Mol Pharmacol Date: 2017 Impact factor: 3.339
Authors: Stephan Buch; Felix Stickel; Eric Trépo; Michael Way; Alexander Herrmann; Hans Dieter Nischalke; Mario Brosch; Jonas Rosendahl; Thomas Berg; Monika Ridinger; Marcella Rietschel; Andrew McQuillin; Josef Frank; Falk Kiefer; Stefan Schreiber; Wolfgang Lieb; Michael Soyka; Nasser Semmo; Elmar Aigner; Christian Datz; Renate Schmelz; Stefan Brückner; Sebastian Zeissig; Anna-Magdalena Stephan; Norbert Wodarz; Jacques Devière; Nicolas Clumeck; Christoph Sarrazin; Frank Lammert; Thierry Gustot; Pierre Deltenre; Henry Völzke; Markus M Lerch; Julia Mayerle; Florian Eyer; Clemens Schafmayer; Sven Cichon; Markus M Nöthen; Michael Nothnagel; David Ellinghaus; Klaus Huse; Andre Franke; Steffen Zopf; Claus Hellerbrand; Christophe Moreno; Denis Franchimont; Marsha Y Morgan; Jochen Hampe Journal: Nat Genet Date: 2015-10-19 Impact factor: 38.330