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

## TL;DR

This study finds that certain genetic variations in the PNPLA3 gene are linked to liver injury markers in patients who naturally clear hepatitis C virus.

## Contribution

The study identifies specific PNPLA3 intronic polymorphisms associated with liver injury in spontaneously cleared HCV patients.

## Key findings

- PNPLA3 intronic polymorphisms AA-rs4823173, GG-rs2896019, and AA-rs2281135 are linked to higher liver injury markers in spontaneously cleared HCV patients.
- The risk haplotype AGA is associated with elevated AST and ALT levels and lower platelet counts in spontaneously cleared HCV patients.
- These polymorphisms are in perfect linkage disequilibrium and may help identify hepatic injury in HCV-negative patients.

## Abstract

Genetic variation in PNPLA3 influences liver fat accumulation and hepatocellular injury in various liver diseases. However, the role of PNPLA3 intronic polymorphisms in hepatic damage among hepatitis C virus (HCV) patients remains unclear. This study aims to investigate the association of three intronic PNPLA3 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. PNPLA3 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 (p < 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 (p < 0.05) in SC patients. PNPLA3 intronic polymorphisms and their association with serum liver injury markers could help identify hepatic injury in HCV-negative patients.