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CYP genetic variants and toxicity related to anti-tubercular agents: a systematic review and meta-analysis

Marty Richardson1, Jamie Kirkham2, Kerry Dwan3

  • 1Department of Biostatistics, University of Liverpool, Liverpool, L69 3GB, UK. mhr@liverpool.ac.uk.

Systematic Reviews
|November 22, 2018
PubMed
Abstract

Insights

This study found that certain CYP2E1 gene variations are linked to anti-tuberculosis drug-induced liver damage. Understanding these genetic factors may help predict and prevent adverse drug reactions in patients undergoing tuberculosis treatment.

Area of Science:

  • Pharmacogenomics
  • Tuberculosis treatment
  • Drug toxicity

Background:

  • Anti-tuberculosis drugs can cause severe adverse effects.
  • Genetic factors, including CYP gene polymorphisms, may influence drug toxicity.
  • Understanding these associations is crucial for patient safety.

Purpose of the Study:

  • To systematically review and meta-analyze evidence on the association between CYP genetic variants and anti-tuberculosis drug toxicity.
  • To synthesize findings from multiple studies to provide a comprehensive overview.

Main Methods:

  • Conducted a systematic search of major scientific databases (MEDLINE, PubMed, EMBASE, BIOSIS, Web of Science).
  • Performed meta-analyses to estimate the effect of each genetic variant on toxicity outcomes.
  • Stratified analyses by country and qualitatively assessed study quality.

Main Results:

  • Included data from 28 distinct patient cohorts.
  • Found significant associations between CYP2E1 RsaI polymorphism and reduced hepatotoxicity risk (OR=0.75).
  • Identified a significantly increased hepatotoxicity risk with the CYP2E1 96-bp deletion-insertion polymorphism (OR=8.20).

Conclusions:

  • Coverage of the association between CYP gene SNPs and anti-tuberculosis drug toxicity is incomplete.
  • Specific CYP2E1 gene polymorphisms (RsaI, 96-bp deletion-insertion) are significantly associated with anti-tuberculosis drug-related hepatotoxicity.
  • Limited ethnicity data prevented analysis of ethnic impact on these associations.
Keywords:
Meta-analysisPharmacogeneticsToxicityTuberculosis

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