PNPLA3 polymorphisms (rs738409) and non-alcoholic fatty liver disease risk and related phenotypes: a meta-analysis

J Gastroenterol Hepatol. 2015 May;30(5):821-9. doi: 10.1111/jgh.12889.

Abstract

Background and aim: One single-nucleotide polymorphisms (SNPs) rs738409 in the patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD) across different populations. One meta-analysis confirmed this association, but within it, only two Asian studies were included. This meta-analysis aimed to investigate the association in Asian population.

Methods: All eligible case-control studies were identified by searching through PubMed and Chinese language databases (CNKI and WanFang) up to July 1, 2014. Pooled estimates (odds ratio [OR] and standardized mean difference) were used to assess the strength of associations in fixed or random-effects models.

Results: A total of 12 studies with 4495 cases and 7431 controls were included. SNP rs738409 G allele was confirmed as a risk factor for NAFLD (G allele vs C allele: OR = 1.92, 95% confidence interval [95%CI]: 1.54-2.39). In addition, based on studies with certain clinical measurements data, G allele carriers were more likely to have higher level of serum alanine aminotransferase (ALT) (standard mean difference [SMD] = 7.03, 95% CI: 2.47-11.60), and higher fibrosis score (SMD = 0.39, 95% CI: 0.18-0.60).

Conclusion: This study provided evidence of SNP rs738409 G allele as a strong risk factor of NAFLD susceptibility and higher level of serum ALT in Asian population.

Keywords: ALT; Asian population; NAFLD; PNPLA3; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alleles
  • Asian People / genetics
  • Case-Control Studies
  • Databases, Bibliographic
  • Fibrosis
  • Genetic Association Studies*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Lipase / genetics*
  • Liver / pathology
  • Membrane Proteins / genetics*
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Phenotype*
  • Polymorphism, Single Nucleotide / genetics*
  • Risk
  • Risk Factors

Substances

  • Membrane Proteins
  • Alanine Transaminase
  • Lipase
  • adiponutrin, human