The Association of PNPLA3, COX-2 and DHCR7 Polymorphisms with Advanced Liver Fibrosis in Patients with HCV Mono-Infection and HCV/HIV Co-Infection

Abstract

There is increasing evidence that host genetic variations may influence the natural history of chronic hepatitis C virus<br />(HCV) infection. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs)<br />of PNPLA3 (rs738409), COX-2 (rs689465) and DHCR7 (rs12785878) and advanced liver fibrosis in Thai patients. A<br />total of 220 patients with HCV mono-infection, 200 patients with HCV/HIV co-infection and 200 healthy controls were<br />enrolled. The SNPs were detected by allelic discrimination using real-time PCR with TaqMan probes. Liver stiffness<br />measurement (LSM) was assessed by transient elastography. Our results showed that the distribution of the studied<br />SNPs were not significantly different between the HCV mono- and co-infected groups. The frequencies AG and GG<br />genotypes of rs689465 and GG genotype of rs12785878 were less commonly found in the HCV mono- and co-infected<br />groups compare with healthy controls (P<0.01). Among patients with HCV infection, older age, HIV co-infection,<br />GG genotype of rs738409 and GG genotype of rs689465 were independently associated with advanced liver fibrosis<br />(LSM≥9.5 kPa) in multivariate analysis. Moreover, the percentage of patients with advanced liver fibrosis increased<br />significantly along with the accumulated numbers of these risk genotypes. In conclusion, PNPLA3 (rs738409) and<br />COX-2 (rs689465) polymorphisms were associated with advanced liver fibrosis in patients with HCV mono- and<br />co-infection, suggesting that these variants might play an important role in progressive liver fibrosis in these patients.