The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: A meta-analysis

Sheng, Yun-Jian; Wu, Gang; He, Hui; Chen, Wen; Zou, Yongsheng; Li, Qin; Zhong, Li; Huang, Yushan; Deng, Chuiwen

doi:10.1016/j.meegid.2014.01.034

Cited by 29 publications

(31 citation statements)

References 29 publications

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“…The absence of GST activity due to null mutation can lead to accumulation of toxic intermediates leading to liver damage. For the CYP2E1 c1/c1, genotype significant association with hepatotoxicity was found among Asians only, but not Indian, Caucasian and other ethnic populations [15,24].…”

Section: Introductionmentioning

confidence: 83%

Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

Igumnova

Capligina

Krams

et al. 2016

Journal of Infection and Chemotherapy

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Section: Introductionmentioning

confidence: 83%

Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

Igumnova

Capligina

Krams

et al. 2016

Journal of Infection and Chemotherapy

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“…The median age of the total study population was 29 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36) years and 128 (46.9%) patients were women. The median BMI was 20.8 (18.7-22.4) kg/m 2 and 5.7% were severely underweight.…”

Section: Resultsmentioning

confidence: 99%

“…The CYP2E1 c1/c2 polymorphism and ATDH susceptibility were studied widely in several populations [19,21,23,[40][41][42]. Several surveys found an association between the c1/c1 (RsaI + ) variant and the development of ATDH [13,21], but other studies found no associations [19,41,42].…”

Section: Discussionmentioning

confidence: 99%

“…The NAT2 gene was studied widely, and several surveys found an association between the slow acetylator phenotype and ATDH development [10,19,20,22]. The single nucleotide polymorphism (SNP) C-1053T in the CYP2E1 gene, also called c1/c2 or the RsaI variant, is one of the most studied genetic variants that is also associated with ATDH susceptibility [21,23]. Deficiency in GST activity, caused by glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null mutations, was associated with idiosyncratic DILI from a large variety of drugs [24] and ATDH development [18,25].…”

Section: Introductionmentioning

confidence: 99%

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Effect of gene–gene and gene–environment interactions associated with antituberculosis drug-induced hepatotoxicity

Chamorro

Castagnino

Aidar

et al. 2017

Pharmacogenetics and Genomics

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a Objectives This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.Patients and methods We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for ATDH development. Polymorphisms were detected using gene sequencing, PCR, and PCR-restriction fragment length polymorphisms. A binary logistic regression analysis was carried out to compare the results of TB patients with and without the development of hepatotoxicity. The multifactor dimensionality reduction method was used to examine genetic and environmental interactions in association with ATDH.Results This study suggests that the slow acetylator profile [odds ratio (OR): 3.02; 95% confidence interval (CI): 1.82-5.00; P < 0.001], genotypes carrying the c2 variant (OR: 2.16; 95% CI: 1.33-3.51; P = 0.002) or the A4 variant of CYP2E1 (OR: 2.13; 95% CI: 1.06-4.29; P = 0.050), and female sex (OR: 1.94; 95% CI: 1.20-3.14; P = 0.006) were independent predictor variables for ATDH. Patients carrying the slow acetylator profile and the c2 variant showed an increased risk (OR: 7.068; 95% CI: 3.34-14.95; P < 0.001).We also identified a synergic interaction (epistasis) between GSTT1 and CYP2E1 associated with an increased risk for ATDH. A meaningful gene-environment interaction was associated with an increased risk of ATDH [testing balance accuracy = 0.675 (P = 0.001) and cross-validation consistency = 10/10].Conclusion ATDH is a severe and prevalent adverse drug reaction and leads to drug discontinuation in 11% of TB patients. Our study created a prediction model that properly classified the 67.5% of TB patients in their risk of developing ATDH. The considerable number of TB patients in our country supports the use of pharmacogenetic testing and a comprehensive clinical history to identify patients with a high risk of suffering hepatotoxicity. Pharmacogenetics and Genomics 00:000-000

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“…Se ha reportado que el gen CYP2E1 tiene varios polimorfismos, pero solo uno (rs2031920 (-1053 C>T)) ha sido extensamente evaluado en asociación con las drogas antituberculosas, este polimorfismo puede afectar la actividad de la enzima (31,35) . El genotipo (C/C) ha sido asociado a la reducción de actividad metabólica (metabolizador lento) de CYP2E1 y así causando un alto riesgo de hepatotoxicidad.…”

Section: Cyp2e1unclassified

Rol de la farmacogenómica en el régimen de tratamiento de tuberculosis

Guio

Levano

Sánchez

et al. 2015

Rev Peru Med Exp Salud Publica

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The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: A meta-analysis

Cited by 29 publications

References 29 publications

Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

Effect of gene–gene and gene–environment interactions associated with antituberculosis drug-induced hepatotoxicity

Rol de la farmacogenómica en el régimen de tratamiento de tuberculosis

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