Linked Intronic Polymorphisms of the PNPLA3 Gene Are Associated with Serum Markers of Liver Injury in Patients with Spontaneous HCV Clearance

Genetic variation in <i>PNPLA3</i> influences liver fat accumulation and hepatocellular injury in various liver diseases. However, the role of <i>PNPLA3</i> intronic polymorphisms in hepatic damage among hepatitis C virus (HCV) patients remains unclear. This study aims to investigate the association of three intronic <i>PNPLA3</i> polymorphisms (rs4823173, rs2896019, and rs2281135) with liver injury in HCV-infected patients with spontaneous HCV clearance (SC) and chronic hepatitis C (CHC). A total of 218 HCV-positive individuals were classified into SC (n = 64) or CHC (n = 154) groups. <i>PNPLA3</i> genotypes were determined by qPCR using TaqMan probes and liver damage through serum markers, noninvasive index, and liver stiffness. Among SC patients, the genotypes AA-rs4823173, GG-rs2896019, and AA-rs2281135 were associated with higher AST, ALT, and APRI, as well as decreased platelet counts, compared with patients homozygous for the non-risk genotypes (<i>p</i> < 0.05). No associations were found in CHC patients. The three polymorphisms were in perfect linkage disequilibrium (r² = 1). The risk haplotype AGA was associated with higher AST and ALT, as well as lower platelet counts (<i>p</i> < 0.05) in SC patients. <i>PNPLA3</i> intronic polymorphisms and their association with serum liver injury markers could help identify hepatic injury in HCV-negative patients.