Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Study on CYP2E1 gene polymorphism and the relationship between methylation level of its promoter region and liver injury induced by anti-tuberculosis drugs in Mongolian tuberculosis patients in Inner Mongolia / 医学研究生学报

ObjectiveThere are few studies on whether the occurrence of anti-tuberculosis drug-induced liver injury (ADIH) is associated with the polymorphism of CYP2E gene and methylation level. This study aims to CYP2E1 gene polymorphism and the relationship between the methylation level of the promoter region and ADIH in Mongolian tuberculosis (TB) patients.Methods A total of 135 Mongolian TB patients who received standardized treatment at the Tuberculosis Research Institute of Tongliao City, Inner Mongolia from November 2015 to June 2018 were selected. According to the ADIH criteria, TB patients with liver injury were selected as the ADIH group (n=45), and TB patients without liver injury were matched as the control group based on a ratio of 1∶2 (n=90). DNA extraction and polymerase chain reaction (PCR) were performed to amplify the CYP2E1 gene to determine the CYP2E1 rs2031920 genotype, and to analyze the CYP2E1 gene polymorphism and relationship between ADIH and promoter methylation level.Results There were no significant differences in the distribution of CYP2E1 rs2031920 genotype, C1 and C2 gene frequencies between the ADIH group and the control group (P>0.05). The overall methylation level in the promoter region of CYP2E1 gene in ADIH group (0.711±0.085) was significantly lower than that of the control group (0.759±0.062). Results of Logistic regression showed that the overall methylation level in the promoter region of CYP2E1 gene was the influencing factor for the occurrence of ADIH (P<0.005). For each 0.1 unit increase of methylation level, the risk of ADIH occurrence reduced by 0.388 times, and the OR (95% CI) value was 0.388 (between 0.204 and 0.739).Conclusion The overall methylation level in the promoter region of CYP2E1 gene was reduced in Mongolian ADIH patients, but the polymorphism of CYP2E1 gene was not related to the occurrence of ADIH. These results suggested that CYP2E1 methylation could be applied to the prevention and treatment of ADIH in patients with tuberculosis.

Transgenic plants of Petunia hybrida harboring the CYP2E1 gene efficiently remove benzene and toluene pollutants and improve resistance to formaldehyde

The CYP2E1 protein belongs to the P450 enzymes family and plays an important role in the metabolism of small molecular and organic pollutants. In this study we generated CYP2E1 transgenic plants of Petunia using Agrobacterium rhizogenes K599. PCR analysis confirmed that the regenerated plants contained the CYP2E1 transgene and the rolB gene of the Ri plasmid. Southern blotting revealed the presence of multiple copies of CYP2E1 in the genome of transgenic plants. Fluorescent quantitative PCR revealed exogenous CYP2E1 gene expression in CYP2E1 transgenic plants at various levels, whereas no like expression was detected in either GUS transgenic plants or wild-types. The absorption of benzene and toluene by transgenic plants was analyzed through quantitative gas chromatography. Transgenic plants with high CYP2E1 expression showed a significant increase in absorption capacity of environmental benzene and toluene, compared to control GUS transgenic and wild type plants. Furthermore, these plants also presented obvious improved resistance to formaldehyde. This study, besides being the first to reveal that the CYP2E1 gene enhances plant resistance to formaldehyde, also furnishes a new method for reducing pollutants, such as benzene, toluene and formaldehyde, by using transgenic flowering horticultural plants.

Genetic polymorphism of alcohol-metabolizing enzyme and alcohol dependence in Polish men

Alcohol dependence poses a serious medical and sociological problem. It is influenced by multiple environmental and genetic factors, which may determine differences in alcohol metabolism. Genetic polymorphism of the enzymes involved in alcohol metabolism is highly ethnically and race dependent. The purpose of this study was to investigate the differences, if present, in the allele and genotype frequency of alcohol dehydrogenase 1B (ADH1B), ADH1C and the microsomal ethanol-oxidizing system (MEOS/CYP2E1) between alcohol-dependent individuals and controls and also to determine if these genotypes cause a difference in the age at which the patients become alcohol dependent. The allele and genotype frequencies of ADH1B, ADH1C, and CYP2E1 were determined in 204 alcohol dependent men and 172 healthy volunteers who do not drink alcohol (control group). Genotyping was performed by PCR-RFLP methods on white cell DNA. ADH1B*1 (99.3 percent) and ADH1C*1 (62.5 percent) alleles and ADH1B*1/*1 (N = 201) and ADH1C*1/*1 (N = 85) genotypes were statistically more frequent among alcohol-dependent subjects than among controls (99.3 and 62.5 percent, N = 201 and 85 vs 94.5 and 40.7 percent, N = 153 and 32, respectively). Differences in the CYP2E1 allele and genotype distribution between groups were not significant. The persons with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes became alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes (28.08, 25.67 years vs 36.0, 45.05, 34.45 years, respectively). In the Polish men examined, ADH1C*1 and ADH1B*1 alleles and ADH1C*1/*1 and ADH1B*1/*1 genotypes favor alcohol dependence. The ADH1B*2 allele may protect from alcohol dependence. However, subjects with ADH1C*1/*1 and CYP2E1*c1/*c2 genotypes become alcohol dependent at a considerably younger age than the subjects with ADH1C*1/*2, ADH1C*2/*2 and CYP2E1*c1/*c1 genotypes.

Functional polymorphism of CYP2E1 gene and alcohol use disorders in a Tibetan population / 中南大学学报(医学版)

Objective To investigate the relationship between the CYPphism and alcohol use disorders, and the potential influence of the CYP2E1 * c1/* c2 polymorphismon the severity and dimensions of alcohol use disorders in Tibetan. Methods Three hundred and forty Tibetans with Alcohol Use Disorders Identification Test (AUDIT) score I>10 and another 315 matched control subjects with AUDIT score ≤5 were enrolled. The CYP2E1 * c1/* c2 polymorphism was de-termined by the standard PCR-RFLP method. Results The frequency of the CYP2E1 * c2 allele in subjects with alcohol use disorders ( 16. 2 % ) was significantly higher than that of the controls(10.8%) , with a P value of 0. 005 and OR value of 1.60 (95% CI: 1.15～2.21). There was also a significant difference in genotype frequencies between the 2 groups ( χ2= 8.75, P = 0.01).Subjects with alcohol use disorders had higher frequencies of genotypes with at least one copy of allele c2 (28.5% vs. 18.7%; χ2=8.65, P=0.003; 0R=1.73) than the control group. The associ-ation of CYP2E1 * c2 allele with alcohol use disorders was much stronger in males than in females,with a male OR value of 2.30. CYP2E1 * c2 allele was associated with increased alcohol consumption and alcohol use disorders in males. Conclusion There is the positive association among CYP2E1 * c2 allele, alcohol use disorders, and the amount of alcohol consumption in Tibetan population.

Expression of cyp2e1 gene in liver tissue in patients with hepatic cirrhosis and obstuctive jaundice / 第二军医大学学报

In order to compare the difference of cyp2e1 gene expression between patients with hepatic cirrhosis and obstructive jaundice,and to investigate the pharmacologic significance behind this difference,liver samples were obtained from patients undergoing hepatic surgery with hepatic cirrhosis( n =7),obstructive jaundice( n =6) and normal tissue of hepatic angioma (controls, n =6). Total hepatic RNA were extracted using the one step method, cyp2e1 cDNA probe prepared by primer randomly marked method, and difference of cyp2e1 expression was compared among patients by Northern blotting.Compared with control group, the expressions of cyp2e1 in liver tissue among patients with obstructive jaundice were evidently reduced, while expression of this gene in cirrhosis liver was unaltered. CYP2E1 isoenzyme encoded by cyp2e1 decreased among patients with obstructive jaundice as expression of cyp2e1 gene significantly reduced, liver ability for metabolism of inhalant anesthetics declined consequently, under some special conditions, hepato nephric toxicity of anesthetics might be aggravated.