Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: a systematic review and meta-analysis

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is known to be the leading cause of chronic liver disease worldwide. This study aims to systematically review and meta-analyze the association between PNPLA3 rs738409 polymorphism and non-alcoholic fatty liver. Methods Following a systematic review and meta-analysis method, articles without any time limitation, were extracted from SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed and ScienceDirect international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the I2 index and using Comprehensive Meta-Analysis software. Results The odds ratio of CC genotype in patients with non-alcoholic fatty liver demonstrates the protective effect of CC genotype with the ratio of 0.52, whereas CG genotype presents an increasing effect of CG genotype with the ratio of 0.19, and GG genotype also showed an increasing effect of GG genotype with the ratio of 1.05. Moreover, CG + GG genotypes as a single group demostrated an odds rartio of 0.88. Conclusion This meta-analysis highlights that people with CC genotype has 52% lower chance of developing non-alcoholic fatty liver disease, and those with CG genotype had 19% higher risk of developing non-alcoholic fatty liver. Those with GG genotype were 105% more likely to develop non-alcoholic fatty liver than others. Moreover, those present in a population with CG + GG genotypes were 88% more likely to have non-alcoholic fatty liver disease.

Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches

“…Further GWAS studies have replicated the correlation of rs738409 C>G p.I148M with steatosis, fibrosis and NAFLD disease severity [ 212 , 213 , 214 ]. A recent meta-analysis suggested that patients with GG genotype are 105% more likely to develop NAFLD than patients who had other genotypes (OR 2.5, 95% CI, 1.64–2.56) [ 215 ]. Rs738409 is now considered an established genetic biomarker for NAFLD, with G-allele carriers also being at risk of liver failure and liver-related fibrosis mortality, as well as developing hepatocellular carcinoma [ 216 ].…”

Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative Review

“…The variants are correlated with the release of pro-inflammatory and pro-fibrogenic cytokines such as chemokine ligand 5, monocyte chemoattractant protein-1, IL-8, granulocyte-macrophage colony-stimulating factor, and TNF-α [81] . Individuals harbouring the rs738409 variant had greater inflammatory infiltration than individuals with wild- type genotypes [ 84 ] . Accordingly, the culture medium of cells expressing the genetic variants was also shown to recruit more immune cells than the wild-type carriers [ 81 ] .…”

Race and Ethnicity in Non-Alcoholic Fatty Liver Disease (NAFLD): A Narrative Review

“…Patatin-like phospholipase domain-containing protein 3 ( PNPLA3 ) is a lipid droplet-associated protein that hydrolases triglycerides and retinyl esters [ 100 ] in adipocytes and hepatocytes, in which it helps regulate both lipogenesis and lipolysis [ 101 , 102 ]. The expression of the PNPLA3 gene decreases during fasting and increases after eating, suggesting a role for PNPLA3 protein in processing and storing fats in the diet [ 103 ].…”