PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C

Javier Ampuero, José A. Del Campo, Lourdes Rojas, José R. García-Lozano, Ricard Solá, Raúl Andrade, José A. Pons, José M. Navarro, José L. Calleja, María Buti, María F. González-Escribano, Xavier Forns, Moisés Diago, Javier García-Samaniego, Manuel Romero-Gómez*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


Background. Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population. Aim. Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients. Material and methods. We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR. Results. PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2). Conclusion. PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection.

Original languageEnglish
Pages (from-to)356-363
Number of pages8
JournalAnnals of Hepatology
Issue number4
Publication statusPublished - 2014


  • Dyslipidemia
  • Huh7.5 cells
  • Liver biopsy
  • Single nucleotide polymorphism
  • Viral replication


Dive into the research topics of 'PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C'. Together they form a unique fingerprint.

Cite this