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Impact of glutathione transferases genes polymorphisms in nevirapine adverse reactions: a possible role for GSTM1 in SJS/TEN susceptibility.

Authors: Ciccacci, Cinzia  Latini, Andrea  Politi, Cristina  Mancinelli, Sandro  Marazzi, Maria C  Novelli, Giuseppe  Palombi, Leonardo  Borgiani, Paola 
Citation: Ciccacci C, etal., Eur J Clin Pharmacol. 2017 Oct;73(10):1253-1259. doi: 10.1007/s00228-017-2295-2. Epub 2017 Jul 8.
Pubmed: (View Article at PubMed) PMID:28689274
DOI: Full-text: DOI:10.1007/s00228-017-2295-2

PURPOSE: Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions.
METHODS: We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP. A case/control association study was performed. We also counted the number of risk alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes.
RESULTS: Among patients, 27 had developed SJS/TEN and 76 had developed hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This association is also observed when other risk factors are taken into account, by a multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting analysis revealed a significantly higher risk for SJS/TEN in patients carrying three or four risk alleles. Moreover, all subjects with five or six risk alleles developed SJS/TEN, while subjects without any risk alleles were present only in the control group.
CONCLUSIONS: We observed an association between GSTM1 and SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a genetic risk profile for SJS/TEN susceptibility.


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RGD Object Information
RGD ID: 14700974
Created: 2019-08-30
Species: All species
Last Modified: 2019-08-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.