Systematic review with meta‐analysis: the I148M variant of patatin‐like phospholipase domain‐containing 3 gene ( PNPLA3 ) is significantly associated with alcoholic liver cirrhosis

Summary 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 ( PNPLA 3 ). 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 PNPLA 3 and ALD and meta‐analysis was conducted in a random‐effects model. Calculations of the odds ratios ( OR s) and their confidence intervals ( CI s), 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 PNPLA 3 is clearly associated with alcoholic liver cirrhosis .