Expression of common housekeeping genes is affected by disease in human hepatitis C virus-infected liver

Mario Congiu1, John L Slavin, Paul V Desmond

  • 1Department of Gastroenterology, St Vincent's Hospital Melbourne, Fitzroy, Vic., Australia.

Insights

Hepatitis C virus (HCV) infection impacts common housekeeping genes (HKGs). Beta-glucuronidase and splicing factor arginine/serine-rich 4 are the most stable HKGs for gene expression studies in HCV-infected human liver.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Virology

Background:

  • Accurate gene expression analysis in hepatitis C virus (HCV)-infected liver relies on stable housekeeping genes (HKGs).
  • Limited data exist on how liver disease severity affects classic HKG expression in HCV patients.

Purpose of the Study:

  • To identify stable HKGs for gene expression studies in human HCV-infected liver across various disease stages.
  • To evaluate the expression stability of commonly used HKGs under different liver disease conditions.

Main Methods:

  • Real-time PCR was used to measure the expression of six candidate HKGs (β-actin, HPRT1, GAPDH, splicing factor arginine/serine-rich 4, β-glucuronidase, 18S rRNA) in liver biopsy tissues.
  • Liver samples were categorized by inflammation, fibrosis, and steatosis, and grouped into mild or severe disease.
  • Gene expression stability was analyzed using statistical programs including NormFinder, BestKeeper, and geNorm.

Main Results:

  • All tested HKGs showed good performance in samples with low disease activity.
  • Hypoxanthine phosphoribosyltransferase 1 (HPRT1), β-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and 18S ribosomal RNA (18S rRNA) exhibited poor stability in samples with severe fibrosis or inflammation.
  • β-glucuronidase and splicing factor arginine/serine-rich 4 demonstrated the highest stability across the spectrum of liver disease severity.

Conclusions:

  • Liver disease significantly affects the expression levels of commonly used HKGs in HCV-infected human liver.
  • β-glucuronidase and splicing factor arginine/serine-rich 4 are recommended as the most reliable HKGs for accurate gene expression studies in this context.
Abstract

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