BACKGROUND The role of the patatin-like phospholipase domain-containing 3 (PNPLA3) single-nucleotide polymorphism (SNP), rs738409, in the development and progression of nonalcoholic fatty liver disease (NAFLD) has not been studied in the Korean population.

AIMS The aim of the study was to investigate the genotype frequency and allele distribution of PNPLA3 rs738409 and the association between the SNP and development of NAFLD and liver fibrosis.

METHODS A total of 339 Korean adults (155 NAFLD patients and 184 healthy controls) were enrolled. PNPLA3 SNP genotyping was carried out using a TaqMan allelic discrimination assay. Liver fibrosis severity was evaluated by NAFLD fibrosis score (NFS) and BARD score.

RESULTS The frequencies of the PNPLA3 rs738409 genotypes, CC, CG, and GG in the healthy control group were 29.9, 50.0, and 20.1%, respectively, and those in NAFLD patients were 20.0, 48.4, and 31.6%, respectively, showing a higher frequency of the risk allele (G allele) (p = 0.006). Among the NAFLD patients, the CG+GG genotype frequency was significantly higher in patients with advanced fibrosis, defined as NFS ≥ -1.455 or BARD score ≥2, than in patients with mild-to-moderate fibrosis (p = 0.012 and p = 0.046, respectively). In multivariate analysis, the CG+GG genotype was an independent factor for NAFLD development (odds ratio 2.568, 95% CI 1.109-5.945, p = 0.028) and for advanced liver fibrosis according to the criteria of NFS ≥ -1.455 (odds ratio 18.573, 95% CI 2.035-169.526, p = 0.010) or a BARD score ≥2 (odds ratio 4.040, 95% CI 1.084-15.048, p = 0.037).

CONCLUSION The PNPLA3 rs738409 polymorphism is common and may confer a significant risk of NAFLD and advanced liver fibrosis in the Korean population.