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Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity

Hari Om Singh1, Sushma Jadhav1, Dharmesh Samani1

  • 11Department of Molecular Biology, National AIDS Research Institute, Pune, India; 2Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, 226014-Lucknow, India.

Current Genomics
|September 27, 2019
PubMed
Abstract

Insights

Single nucleotide polymorphisms in microRNA genes, specifically miR196a, are associated with an increased risk of nevirapine-induced hepatotoxicity in HIV patients. Certain genotypes like miR196aC/T and combined genotypes GCT and CCC may facilitate this risk.

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Hepatology

Background:

  • MicroRNAs (miRNAs) regulate gene expression and influence drug efficacy and toxicity.
  • Single nucleotide polymorphisms (SNPs) within miRNA genes can alter their function.
  • Understanding miRNA gene variations is crucial for personalized medicine, particularly in managing drug-induced liver injury.

Purpose of the Study:

  • To investigate the association between specific miRNA polymorphisms (miR-146a, miR-149, miR-196a) and the risk of hepatotoxicity.
  • To evaluate the role of these polymorphisms in HIV patients undergoing treatment with nevirapine.
  • To determine if alcohol consumption interacts with miRNA genotypes to affect hepatotoxicity risk.

Main Methods:

  • Genotyping of miR-146a G/C, miR-149 C/T, and miR-196a C/T polymorphisms using the PCR-RFLP method.
  • Study population included 34 patients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls.
  • Statistical analysis, including odds ratios (OR) and P-values, was used to assess associations.

Main Results:

  • miR196aCT and combined GCT genotypes showed a borderline significant risk for hepatotoxicity severity.
  • Combined genotypes CCC and GCT were associated with susceptibility to hepatotoxicity when compared to healthy controls.
  • miR196TT genotype was linked to advanced HIV disease stage.
  • miR196aCT genotype indicated a susceptibility to hepatotoxicity acquisition in HIV patients who consumed alcohol.
  • miR149TT and miR196aTT genotypes were associated with hepatotoxicity risk in HIV patients not experiencing hepatotoxicity.
  • miR196aCT genotype showed a significant independent risk factor for hepatotoxicity severity in multivariate analysis.

Conclusions:

  • miR196aC/T polymorphism, along with combined GCT and CCC genotypes, may increase the risk of acquiring and experiencing severity of nevirapine-induced hepatotoxicity.
  • The study highlights the potential role of miRNA gene variations in predicting drug-induced liver injury in HIV patients.
  • Further research is warranted to validate these findings and explore therapeutic strategies based on pharmacogenomic profiles.
Keywords:
ARV- associated hepatotoxicityGenetic predispositionHIV patientsNNRTI regimenmiRNA polymorphisms

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