PNPLA3 gene polymorphism and severity of liver steatosis and fibrosis

Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases worldwide. Environmental and genetic factors have an impact on NAFLD development. Single nucleotide polymorphism in the PNPLA3 gene is strongly related to the increased fat content in hepatocytes. The aim of our study was to investigate the association between PNPLA3 variants and the intensity of liver steatosis and fibrosis assessed by liver biopsy in patients with NAFLD. Material and methods: The study group comprised 127 patients with NAFLD confirmed by liver biopsy. The control group comprised 251 healthy volunteers. In every case genotyping of the PNPLA3 rs738409 C to G nonsynonymous sequence variant was performed. Distributions of genotypes and alleles were compared between NAFLD patients and controls, and analyzed in relation to different steatosis and fibrosis stages in the study group. Results: Frequencies of PNPLA3 genotypes strongly differ between NAFLD patients and controls (p = 0.00001). Odds ratio (OR) for genotype GG in NAFLD was 2.94 (1.45–5.97, p = 0.0015). Also allele G was more frequent in NAFLD patients vs. controls (p = 0.00001); OR for G allele in NAFLD was 2.74 (1.77–4.27, p = 0.00000273). No significant differences in the genotype or allele distribution of PNLPA3 were observed in relation to steatosis intensity or between patients with or without cirrhosis. However, allele G was found is every hepatocellular carcinoma case. Conclusions: We do not advocate universal genetic testing in every NAFLD case to select patients at risk of development of cirrhosis or steatohepatitis. Further investigation of the relationship between PNPLA3 variants and hepatocellular carcinoma is warranted.