Digestive Diseases and Sciences

, Volume 63, Issue 11, pp 2969–2974 | Cite as

PNPLA3 Gene Polymorphisms in HCV/HIV-Coinfected Individuals

  • Kenneth E. ShermanEmail author
  • Susan D. Rouster
  • Minhee Kang
  • Triin Umbleja
  • Richard Sterling
  • Adeel A. Butt
  • For the ACTG 5294 BIRTH Study Team
Original Article


Background and Aims

The patatin-like phospholipase domain-containing 3 (PNPLA3) gene has been associated with the development of alcoholic and nonalcoholic steatohepatitis. Using a newly developed and validated assay for PNPLA3, we explored the prevalence of gene polymorphisms in a cohort of HCV/HIV-coinfected individuals to determine whether there was an association with insulin resistance or hepatic fibrosis.


A high-resolution melting point (HRM) assay was developed and validated. The assay was used to evaluate samples obtained in the context of a clinical trial performed at ACTG sites across the USA in HIV-infected patients. Clinical features and treatment outcomes were assessed in relation to the PNPLA3 genotype.


The HRM methodology demonstrated 100% concordance with results obtained by Sanger sequencing. Among 241 participants tested, 66.0% had the wild-type allele (CC) and the remainder had the aberrant PNPLA3 gene polymorphism in the homozygotic (GG) or heterozygotic (CG) form. Race and ethnicity were associated with PNPLA3 genotype but fibrosis stage, Homeostatic Model Assessment of Insulin Resistance, and HCV treatment outcome were not.


The HRM method is an effective, rapid technique for characterizing PNPLA3 genotype. In those with HCV/HIV infection, nearly 40% carry gene polymorphisms associated with the development of NASH or ASH. Prospective studies should focus on this group to determine whether they represent a subset of HIV-infected persons at increased risk of fibrotic progression.


Patatin-like Human immunodeficiency AIDS Fibrosis Steatosis 



ACTG 5294 Supplement Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636, and UM1 AI106701.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kenneth E. Sherman
    • 1
    Email author
  • Susan D. Rouster
    • 1
  • Minhee Kang
    • 2
  • Triin Umbleja
    • 2
  • Richard Sterling
    • 4
    • 5
  • Adeel A. Butt
    • 3
  • For the ACTG 5294 BIRTH Study Team
  1. 1.Division of Digestive DiseasesUniversity of Cincinnati College of MedicineCincinnatiUSA
  2. 2.Harvard TH Chan School of Public HealthBostonUSA
  3. 3.Virginia Commonwealth UniversityRichmondUSA
  4. 4.Weill Cornell Medical CollegeNew YorkUSA
  5. 5.DohaQatar

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