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