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



Richardson, Marty ORCID: 0000-0002-7097-8704, Kirkham, Jamie ORCID: 0000-0003-2579-9325, Dwan, Kerry, Sloan, Derek J, Davies, Geraint ORCID: 0000-0002-3819-490X and Jorgensen, Andrea L ORCID: 0000-0002-6977-9337
(2018) <i>CYP</i> genetic variants and toxicity related to anti-tubercular agents: a systematic review and meta-analysis. SYSTEMATIC REVIEWS, 7 (1). 204-.

Access the full-text of this item by clicking on the Open Access link.
[img] Text
s13643-018-0861-z.pdf - Published version

Download (1MB)

Abstract

<h4>Background</h4>Treatment with anti-tuberculosis drugs may cause patients to experience serious adverse effects. Genetic factors, such as polymorphisms of CYP genes, may increase the likelihood of a patient experiencing such adverse drug reactions. In this systematic review and meta-analysis, we synthesised evidence for associations between CYP genetic variants and anti-tuberculosis drug-related toxicity outcomes.<h4>Methods</h4>We searched MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science to identify relevant studies. We performed meta-analyses to obtain an effect estimate for each genetic variant on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies.<h4>Results</h4>We included data from 28 distinct cohorts of patients in the review. We identified many areas of concern with regard to the quality of included studies. Patients with homozygous mutant-type or heterozygous genotype at the CYP2E1 RsaI polymorphism were significantly less likely to experience hepatotoxicity than patients with homozygous wild-type genotype (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.56-1.00; p = 0.047, I<sup>2</sup> = 58.2%). No significant differences were observed for the CYP2E1 DraI and PstI polymorphisms. For the 96-bp deletion-insertion single-nucleotide polymorphism (SNP) of the CYP2E1 gene, homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (OR = 8.20, 95% CI 1.38-48.68, I<sup>2</sup> = 0%); no significant difference was observed for heterozygous genotype compared with homozygous wild-type (OR = 0.77, 95% CI 0.19-3.21, I<sup>2</sup> = 0%).<h4>Conclusions</h4>Generally, we identified that coverage of the association between SNPs of CYP genes and anti-tuberculosis drug-related toxicity outcomes is incomplete. We observed significant associations between the RsaI and 96-bp deletion-insertion SNPs of the CYP2E1 gene and anti-tuberculosis drug-related hepatotoxicity. We were unable to comment on the impact of ethnicity on the investigated associations, as information on participants' ethnicity was sparsely reported in the included studies.<h4>Systematic review registration</h4>PROSPERO registration number: CRD42017068448.

Item Type: Article
Uncontrolled Keywords: Tuberculosis, Pharmacogenetics, Toxicity, Meta-analysis
Depositing User: Symplectic Admin
Date Deposited: 27 Nov 2018 11:46
Last Modified: 05 Oct 2023 12:54
DOI: 10.1186/s13643-018-0861-z
Open Access URL: https://doi.org/10.1186/s13643-018-0861-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3029099