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

Authors

  • A.-J. Chamorro,

    1. Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
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  • J.-L. Torres,

    1. Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
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  • J.-A. Mirón-Canelo,

    1. Department of Epidemiology, University of Salamanca-IBSAL, Salamanca, Spain
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  • R. González-Sarmiento,

    1. Molecular Medicine Unit-IBSAL, University of Salamanca-SACYL-CSIC, Salamanca, Spain
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  • F.-J. Laso,

    1. Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
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  • M. Marcos

    Corresponding author
    1. Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
    • Correspondence to:

      Dr M. Marcos, Servicio de Medicina Interna, Hospital Universitario de Salamanca, P° San Vicente, 58-156, Salamanca 37007, Spain.

      E-mail: mmarcos@usal.es

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  • As part of AP&T's peer-review process, a technical check of this meta-analysis was performed by Mr M. Siddiqui. This article was accepted for publication after full peer-review.

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 (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.

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