Patatin-like phospholipase domain-containing 3 gene (PNPLA3) polymorphic (rs738409) single nucleotide polymorphisms and susceptibility to nonalcoholic fatty liver disease: A meta-analysis of twenty studies

Abstract

Background: To investigate the correlation between rs738409 polymorphism of patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene (encoding I148m) and genetic susceptibility to nonalcoholic fatty liver disease (NAFLD). Methods: Web of Science, Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform databases were subjected to study retrieving, from the earliest records to November 2022. International databases were searched using the key words (PNPLA3 gene or PNPLA3 polymorphism or patatin-like phospholipase domain-containing pro-tein3) and (nonalcoholic fatty liver disease or NAFLD or nonalcoholic steatohepatitis) and their possible combination. There was no limitation to language. Ethnicity and country restrictions were not applied. Hardy–Weinberg equilibrium about the genotype frequencies of rs738,409 polymorphism in group of controls was assessed using a chi-square goodness-of-fit test (P > .05). A chi-square-based Q test was applied to assess heterogeneity among studies. The random-effect model (DerSimonian–Laird method) was used when a probability value of P < .10, I 2 > 50%. If not, the fixed-effect model (Mantel–Haenszel method) was adopted. The current meta-analysis was done by using STATA 16.0. Results: Twenty studies are selected for this meta-analysis, which includes totally 3240 patients in the treatment group and 5210 patients in the control group. These studies demonstrated a significant increased association between rs738,409 and NAFLD under 5 models: allelic contrast (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.65–2.37, P heterogeneity = 0.000, Z = 7.346, P = .000), homozygote comparison (OR = 3.59, 95% CI = 2.56–5.04, P heterogeneity = 0.000, Z = 7.416, P = .000), heterozygote comparison (OR = 1.93, 95% CI = 1.63–2.30, P heterogeneity = 0.002, Z = 7.507, P = .000), the dominant allele model (OR = 2.33, 95% CI = 1.89–2.88, P heterogeneity = 0.000, Z = 7.856, P = .000), and the recessive allele model (OR = 2.56, 95% CI = 1.96–3.35, P heterogeneity = 0.000, Z = 6.850, P = .000). Subgroup analysis shows that the rs738,409 polymorphism of PNPLA3 gene in Caucasians and those with a sample size of < 300 is significantly associated with the susceptibility to nonalcoholic fatty liver. Sensitivity analysis shows that the results of meta-analysis are stable. Conclusion: PNPLA3 rs738,409 may play a significant role in increasing risk of NAFLD.