Effect of the patatin‐like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of nonalcoholic fatty liver disease and metabolic syndromes: A meta‐analysis of paediatric and adolescent individuals

Abstract

Background: The effect of the patatin-like phospholipase domain containing 3 gene (PNPLA3) I148M polymorphism on the risk and severity of paediatric and adolescent nonalcoholic fatty liver disease (NAFLD) remains inconclusive.Objectives: We aimed to estimate the effect of this polymorphism not only on earlyonset NAFLD risk and severity but also on metabolic syndromes susceptibility.Methods: A systematic literature search was performed to identify relevant datasets.The odds ratio of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals were calculated to assess the strength of the associations.Results: Twenty-seven studies comprising 10 070 subjects were eligible. The summary effect showed that this polymorphism increased susceptibility to NAFLD development. Furthermore, it also indicated that nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers among paediatric and adolescent NAFLD patients. Moreover, the meta-analysis suggested that the variant was significantly associated with elevated liver damage indexes, including serum alanine transaminase, aspartate transaminase, gamma-glutamyltransferase concentrations, and liver fat content. However, the summary estimates for insulin resistance, lipid metabolism, and adiposity showed no significant associations. Conclusions:The PNPLA3 I148M polymorphism is associated with elevated earlyonset NAFLD risk, severity, and liver damage but not with related metabolic syndromes.

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

“…According to a meta-analysis by Jiaying et al (2020), this gene is involved in the development of non-alcoholic osteopathy (NASH) in children and adolescents; it is also accosiated with factors such as serum alanine transaminase, aspartate transaminase, gamma glutamyl transferase, that are indicators of liver damage [51].…”

Identification and Optimization of a Minor Allele-Specific siRNA to Prevent PNPLA3 I148M-Driven Nonalcoholic Fatty Liver Disease

“…Over the last several years, meta-analyses of PNPLA3 I148M carriers versus noncarriers repeatedly conclude that carriers of the variant allele are at increased risk for all stages of NAFLD, including NASH, cirrhosis, and HCC [6,7,65,[72][73][74][75], among the pediatric and adolescent population [2,76], and among lean individuals with NAFLD [77]. NASH is emerging as the leading cause of liver transplant in the developed world.…”

“…T he single nucleotide polymorphism (SNP), in the gene patatin like phospholipase domain containing 3 (PNPLA3), rs738409 (I148M), is associated with hepatic triglyceride content and, over the 10 years since its identification, is now known to be the strongest genetic determinant for all stages of the nonalcoholic fatty liver disease (NAFLD) spectrum: nonalcoholic fatty liver (or steatosis), nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC) [1][2][3][4][5][6][7][8].…”

Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease in School-Age Children and Adolescents in Shenyang, China

“…On one hand, fatty liver may be related to genetic factors, and many genetic variations have been found. Polymorphisms in the PNPLA3 gene can increase liver fat content and the risk of MAFLD and are possibly related to the severity level of MAFLD [21] . The TM6SF2, MBOAT7, and GCKR genes all appear to affect the occurrence and development of MAFLD in children and adolescents [22] .…”