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 Pediatric And Adolescent Individuals

Objective:The effect of the patatin-like phospholipase domain containing 3 gene(PNPLA3)I148M polymorphism on the risk and severity of pediatric and adolescent nonalcoholic fatty liver disease(NAFLD)remains inconclusive.We aimed to estimate the effect of this polymorphism not only on early-onset NAFLD risk and severity,but also on metabolic syndromes’ susceptibility.Methods:A systematic literature search was performed to find studies that disclosed relevant data.Odds ratio for dichotomic variables and standardized mean difference for quantitative variables with corresponding 95%confidence intervals were calculated to assess the strength of associations.Results:Among the 175 studies preliminarily identified,27 comprising 10,070 subjects were eligible for meta-analysis.The summary effect showed the I148M polymorphism might confer increased susceptibility to NAFLD development.Furthermore,the pooled estimates indicated that nonalcoholic steatohepatitis(NASH)was more frequently observed in G allele carriers among pediatric and adolescent NAFLD patients.Moreover,the quantitative synthesis of data suggested the variant was significantly associated with elevated liver damage indexes,including serum alanine transaminase(ALT),aspartate transaminase(AST),gamma-glutamyltransferase(GGT)concentrations,and liver fat content(LFC).However,none of the meta-analyses for fasting glucose(FPG),fasting insulin(FINS)concentrations and homeostasis model assessment-insulin resistance(HOMA-IR)level reflecting insulin resistance,the summary estimates for high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),and triglyceride(TG)mirroring lipid metabolism or the pooled results for body-mass index(BMI)and waist-height ratio(W-Hr)showing adiposity could provide explicit evidence for the significant association with the I148M variant.Conclusions:These results supported that the PNPLA3 I148M polymorphism is associated with elevated pediatric and adolescent NAFLD risk,severity,and liver damage,but not with related metabolic syndromes.