IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease

J Hepatol. 2012 Jun;56(6):1356-62. doi: 10.1016/j.jhep.2012.01.007. Epub 2012 Feb 5.

Abstract

Background & aims: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients.

Methods: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested.

Results: Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorphism, compared with 72 (45%) and 14 (8.8%) with TC and TT variants, respectively. PNPLA3 rs738409 CC polymorphism was present in 47 (29.4%) patients, compared with 79 (49.4%) and 34 (21.3%) with CG and GG variants, respectively. Multivariate logistic regression analysis showed that age (OR 1.043, 95% CI 1.012-1.075, p=0.007), triglycerides (OR 1.005, 95% CI 1.000-1.010, p=0.04), hyperuricemia (OR 5.027, 95% CI 1.839-13.742, p=0.002), IL28B rs12979860 TT/TC (OR 0.219, 95% CI 0.101-0.472, p<0.001), and steatosis grade (OR 1.704, 95% CI 1.048-2.773, p=0.03) were independently linked to moderate-severe lobular inflammation. Finally, IL28B rs12979860 CC was associated with severe fibrosis (F3-F4) on univariate analysis, even if only older age (OR 1.064, 95% CI 1.026-1.104, p=0.001), high HOMA (OR 1.213, 95% CI 1.068-1.377, p=0.003), and lobular inflammation (OR 3.181, 95% CI 1.438-7.036, p=0.004), remained associated in multivariate logistic regression analysis.

Conclusions: In NAFLD patients, IL28B rs12979860 CC genotype, together with PNPLA3 rs738409 GG, is associated with the severity of liver damage.

MeSH terms

  • Adult
  • Cross-Sectional Studies
  • Fatty Liver / genetics
  • Fatty Liver / pathology*
  • Female
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Lipase / genetics*
  • Liver / pathology*
  • Logistic Models
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Polymorphism, Single Nucleotide*

Substances

  • interferon-lambda, human
  • Interleukins
  • Membrane Proteins
  • Interferons
  • Lipase
  • adiponutrin, human