Association of PNPLA3 rs738409 G/C gene polymorphism with nonalcoholic fatty liver disease in children: a meta-analysis

Objective: To systematically review the association of PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease(NAFLD) in children. Design: Systematic review and meta-analysis. Data sources and study selection: We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Data extraction and analyses: First author's surname, publication year, country, total numbers of patients in the case and control groups, sex ratio, and body mass index (BMI), as well as the numbers of cases and controls with the C/C, C/G and G/G genotypes were extracted from the included studies. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. Results: A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR=3.343, 95% CI=1.524-7.334; GG+GC vs CC,OR=3.157, 95% CI=1.446-6.892;GG vs GC+CC,OR=5.692, 95% CI=1.941-16.689; GG+CC vs GC,OR=2.756, 95% CI=1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver(NAFL) and children with nonalcoholic steatohepatitis(NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model(GG vs GC+CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias. Conclusions: Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children. trial registration number： CRD42019134056.