Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study
Abstract
:1. Introduction
2. Materials and Method
2.1. Ethics Regulations
2.2. Sample Size Calculation
2.3. Selection of Experimental Cases and Controls
2.4. Epidemiological Investigation
2.5. Sample Collection and Extraction of Genomic DNA
2.6. Analysis of Gene Polymorphism
2.7. Methylation-Specific PCR Amplification
2.8. Statistical Analysis
3. Results
3.1. Basic Characteristics of the Cases
3.2. Correlation with Gene Polymorphism of the Two Drug-Metabolizing Enzymes and ADLI
3.3. Correlation between CpG Island Methylation of Genes of the Two Drug-Metabolizing Enzymes and ADLI
3.4. Multivariate Analysis of the Correlation between CpG Island Methylation of Genes of the Two Drug Metabolizing Enzymes and Anti-TB Drug-Induced Liver Injury
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Control | Case | Wald χ2 | p Value | OR (95% CI) | |
---|---|---|---|---|---|
CYP2E1 -1019 Mutant Genotype * | CYP2E1 -1019 Wild Genotype | ||||
CYP2E1 -1019 Mutant genotype * | 10 | 24 | 0.667 | 0.414 | 0.694 (0.292–1.650) |
CYP2E1 -1019 Wild genotype | 30 | 50 | |||
CYP2E1 -1259 Mutant genotype * | CYP2E1 -1259 Wild genotype | ||||
CYP2E1 -1259 Mutant genotype * | 16 | 18 | 2.174 | 0.140 | 1.651 (0.731–3.730) |
CYP2E1 -1259 Wild genotype | 28 | 52 | |||
CYP2D6 -188 Mutant genotype * | CYP2D6 -188 Wild genotype | ||||
CYP2D6 -188 Mutant genotype * | 70 | 18 | 0.400 | 0.527 | 0.707 (0.216–2.312) |
CYP2D6 -188 Wild genotype | 22 | 4 | |||
CYP2D6 -4268 Mutant genotype * | CYP2D6 -4268 Wild genotype | ||||
CYP2D6 -4268 Mutant genotype * | 92 | 16 | 6.150 | 0.013 | 0.250 (0.084–0.748) |
CYP2D6 -4268 Wild genotype | 4 | 2 |
Control | Case | Wald χ2 | p Value | OR (95% CI) | |
---|---|---|---|---|---|
CYP2E1 CpG Island Methylated * | CYP2E1 CpG Island Unmethylated | ||||
CYP2E1 CpG island methylated * | 58 | 14 | 7.807 | 0.005 | 2.429 (1.303–4.525) |
CYP2E1 CpG island unmethylated | 34 | 8 | |||
CYP2D6 CpG island methylated * | CYP2D6 CpG island unmethylated | ||||
CYP2D6 CpG island methylated * | 76 | 8 | 9.765 | 0.002 | 3.500 (1.595–7.679) |
CYP2D6 CpG island unmethylated | 28 | 2 |
Variables | S.E. | Wald χ2 | p Value | OR (95% CI) | |
---|---|---|---|---|---|
CYP2E1 CpG island methylated | 1.479 | 0.406 | 13.291 | <0.001 | 4.390 (1.982–9.724) |
CYP2D6 CpG island methylated | 2.218 | 0.528 | 17.635 | <0.001 | 9.193 (3.264–25.888) |
CYP2D6 -4268G/C mutant genotypes | −2.409 | 0.779 | 9.568 | 0.002 | 0.090 (0.020–0.414) |
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Zhang, J.; Zhu, X.; Li, Y.; Zhu, L.; Li, S.; Zheng, G.; Ren, Q.; Xiao, Y.; Feng, F. Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study. Int. J. Environ. Res. Public Health 2016, 13, 776. https://doi.org/10.3390/ijerph13080776
Zhang J, Zhu X, Li Y, Zhu L, Li S, Zheng G, Ren Q, Xiao Y, Feng F. Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study. International Journal of Environmental Research and Public Health. 2016; 13(8):776. https://doi.org/10.3390/ijerph13080776
Chicago/Turabian StyleZhang, Jinling, Xuebin Zhu, Yuhong Li, Lingyan Zhu, Shiming Li, Guoying Zheng, Qi Ren, Yonghong Xiao, and Fumin Feng. 2016. "Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study" International Journal of Environmental Research and Public Health 13, no. 8: 776. https://doi.org/10.3390/ijerph13080776