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  • Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study

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Interferon gamma receptor 2 gene variants are associated with liver fibrosis in the general population: the Rotterdam Study
  1. Elisabeth P C Plompen1,
  2. Bettina E Hansen1,2,
  3. Jeoffrey N L Schouten3,
  4. Sarwa Darwish Murad1,
  5. Daan W Loth4,
  6. Willem Pieter Brouwer1,
  7. Aaron Isaacs5,
  8. Pavel Taimr1,
  9. Albert Hofman4,
  10. Cornelia M van Duijn5,
  11. André G Uitterlinden4,6,
  12. Bruno H C Stricker4,
  13. Frank W G Leebeek7,
  14. Harry L A Janssen1,8
  1. 1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  2. 2 Department of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  3. 3 Department of Gastroenterology and Hepatology, AZ Nikolaas, Sint-Niklaas, Belgium
  4. 4 Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  5. 5 Department of Genetic Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  6. 6 Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  7. 7 Department of Hematology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  8. 8 Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Harry L A Janssen, Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, 399 Bathurst Street, 6B FP, Room 164, Toronto, ON, M5T 2S8, Canada; harry.janssen@uhn.ca

https://doi.org/10.1136/gutjnl-2014-308398

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    Dear Editor,

    Increasing evidence suggests that genetic factors play a role in the multifactorial aetiology of liver fibrosis. In their recent paper, Zhao et al 1 support this by describing the role of the Jnk1 gene in liver fibrogenesis. Previously, the role of other inflammatory-related genes in the development of liver fibrosis has been described in patients with chronic liver diseases. In patients with chronic hepatitis C, Nalpas et al 2 demonstrated a strong association between single nucleotide polymorphisms (SNP) in the interferon gamma receptor 2 (IFNGR2) gene and progression of liver fibrosis. The role of interferon gamma in liver fibrogenesis has been reported before, but the precise mechanism of this effect has not yet been fully elucidated.3 ,4 Currently, it is not known whether the genetic variants in the IFNGR2 gene also influence liver fibrogenesis in individuals without liver disease. Therefore, we aimed to study the association between the IFNGR2 SNPs and liver fibrosis in the general population.

    For this purpose, we assessed the extent of liver fibrosis non-invasively by measuring liver stiffness (LS) using transient elastography (TE) (Fibroscan, Echosens) in 1059 participants of the Rotterdam study. Genotyping in these, almost exclusively Caucasian (99.6%) participants was performed with the Infinium II HumanHap 550K Genotyping Bead-Chip V.3 (Illumina, San Diego, California, USA). The Rotterdam Study is a large, ongoing, prospective population-based cohort study in subjects aged ≥55 years in …

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    Footnotes

    • Contributors Conception or design of the work: EPCP, BEH, JNLS, SDW, DWL, WPB, AI, PT, AH, CMvD, AGU, BHCS, FWGL, HLAJ. Acquisition, analysis, and interpretation of data: EPCP, BEH, JNLS, SDW, DWL, WPB, AI, PT, AH, CMvD, AGU, BHCS, FWGL, HLAJ. Drafting the work or revising it critically for important intellectual content: EPCP, BEH, JNLS, SDW, DWL, WPB, AI, PT, AH, CMvD, AGU, BHCS, FWGL, HLAJ. Final approval of the version to be published: EPCP, BEH, JNLS, SDW, DWL, WPB, AI, PT, AH, CMvD, AGU, BHCS, FWGL, HLAJ. Agreement to be accountable for all aspects of the work: EPCP, BEH, JNLS, SDW, DWL, WPB, AI, PT, AH, CMvD, AGU, BHCS, FWGL, HLAJ.

    • Funding The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII) and by the Municipality of Rotterdam. This study was financially supported by the Foundation for Liver Research (SLO), Rotterdam, The Netherlands.

    • Competing interests None.

    • Ethics approval Medical Ethics Committee of the Erasmus MC University Medical Center.

    • Provenance and peer review Not commissioned; externally peer reviewed.