Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients

Abstract

Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have been shown to accelerate the progression of fibrosis to cirrhosis and to increase the risk of hepatocellular carcinoma. An optimal peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) activity is crucial to prevent NAFLD installation. The present study aims to investigate the associations between two common PPARGC1A polymorphisms (rs8192678 and rs12640088) and the outcomes of HCV infection in a North African context. A series of 592 consecutive Moroccan subjects, including 292 patients with chronic hepatitis C (CHC), 100 resolvers and 200 healthy controls were genotyped using a TaqMan allelic discrimination assay. PPARGC1A variations at rs8192678 and rs12640088 were not associated with spontaneous clearance of HCV infection (adjusted ORs = 0.76 and 0.79 respectively, P > 0.05, for both). Furthermore, multivariable logistic regression analysis showed that both SNPs were not associated with fibrosis progression (OR = 0.71; 95% CI 0.20–2.49; P = 0.739; OR = 1.28; 95% CI 0.25–6.54; P = 0.512, respectively). We conclude that, in the genetic context of South Mediterranean patients, rs8192678 and rs12640088 polymorphisms of PPARGC1A are neither associated with spontaneous clearance nor with disease progression in individuals infected with HCV.

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Acknowledgements

The authors would like to acknowledge all patients for their participation in this study.

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Authors

Contributions

SB, SE, RE conceived, designed the experiments and wrote the paper; SB, SE, MK and PP contributed to the drafting and revision of the article; IZ, FZJ and HC helped in the collection of samples; WB and MT contributed to the clinical data; MEI helped in the statistical analysis; IC and AM helped in the interpretation of data; SB contributed to the final approval of the version to be submitted. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Sayeh Ezzikouri or Soumaya Benjelloun.

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Authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The study was approved by the Ethics Committee of the Faculty of Medicine of Casablanca in accordance with the ethical guidelines of the Declaration of Helsinki. For study participation, written informed consent for genetic testing was obtained from all subjects.

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ElFihry, R., Elmessaoudi-Idrissi, M., Jadid, FZ. et al. Effect of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Alpha Variants on Spontaneous Clearance and Fibrosis Progression during Hepatitis C Virus Infection in Moroccan Patients. Virol. Sin. 35, 566–574 (2020). https://doi.org/10.1007/s12250-020-00220-7

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Keywords

  • Chronic hepatitis C
  • Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)
  • Polymorphisms
  • Disease progression