Annals of Occupational and Environmental Medicine

Original Article

Effect of Genetic Polymorphisms of CYP2E1 and ALDH2 on the Relationship between the Levels of Urinary 8-Hydroxydeoxyguanosine and t,t-Muconic Acid: Yong Dae Kim, Jong Won Kang, Sang Yong Eom, Yan Wei Zhang, Sung Hoon Kim, Eun Young Kim, Chul Ho Lee, Jai Dong Moon, Heon Kim; Korean Journal of Occupational and Environmental Medicine 2007;19(2):164-170. Published online June 30, 2007; DOI: https://doi.org/10.35371/kjoem.2007.19.2.164

Abstract PDF: OBJECTIVES
This study was performed to investigate the effect of genetic polymorphisms on the oxidative genetic damage caused by benzene exposure in workers.
METHODS
We measured urinary t,t-muconic acid levels as a biomarker for benzene exposure and measured the level of urinary 8-OHdG to assess oxidative DNA damage in benzene-exposed healthy male workers. Genetic polymorphisms of ALDH2 and CYP2E1 were determined by TaqMan assay. We estimated Pearson correlation coefficients between urinary t,t-muconic acid and 8-OHdG according to the genetic polymorphisms of CYP2E1 and ALDH2.
RESULTS
There was a significant relationship between urinary t,t-muconic acid and 8-OHdG concentrations in overall subjects (R=0.532, p<0.001). Smokers showed a higher correlation coefficient between the markers than nonsmokers did (R=0.520 vs. 0.010). Individuals with CYP2E1 c1/c1 genotype also showed a higher correlation coefficient between them than those with CYP2E1 c1/c2 or c2/c2 genotypes (R=0.670 vs. -0.145). In multiple linear regression analysis including smoking status, sorbic acid intake, age and genetic polymorphisms of CYP2E1 and ALDH2 as the independent variables, urinary t,t-muconic acid showed a significant association with urinary 8-OHdG.
CONCLUSIONS
There was a significant correlation between urinary 8-OHdG and urinary t,t-muconic acid in benzene-exposed workers. This relationship was affected by genetic polymorphisms of CYP2E1and ALDH2.

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Original Article

The Association between Pneumoconiosis and Genetic Polymorphism of GSTM1, GSTT1, GSTP1, NAT2, CYP2E1 and CYP1A1: Cha Jae Oh, Moon Young Hwang, Kang Jin Lee, Hoo Rak Lee, Byung Mann Cho; Korean Journal of Occupational and Environmental Medicine 2005;17(2):85-94. Published online June 30, 2005; DOI: https://doi.org/10.35371/kjoem.2005.17.2.85

Abstract PDF: OBJECTIVES
To investigate effects of genetic polymorphism of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), glutathione S-transferase P1 (GSTP1), N-acetyltransferase (NAT2), cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A1 (CYP1A1) on pneumoconiosis.
METHODS
Eighty-five pneumoconiosis patients and 122 age and sex matched healthy controls were enrolled. Direct interview and standard questionnaire were conducted and the genotypes of GSTM1, GSTT1, GSTP1, NAT2, CYP2E1 and CYP1A1 were investigated using multiplex PCR or PCR-RFLP methods with DNA extracted from venous blood. The relationship was investigated between the severity of pneumoconiosis and the polymorphism of GSTM1, GSTT1, GSTP1, NAT2, CYP2E1 and CYP1A1, and also with various environmental factors including smoking.
RESULTS
We observed a significantly higher rate of genetic polymorphism in pneumoconiosis patients than in normal subjects. The odds ratio (95% CI) of NAT2 was 2.09 (1.19-3.68). In addition, smoking was related significantly with pneumoconiosis (OR 2.89, 95% CI 1.40-5.95). In multiple logistic regression analyses, NAT2 and smoking were significant risk factors for the development of pneumoconiosis (OR 1.84, 95% CI 1.00-3.37; OR 2.98, 95% CI 1.40-6.35, respectively). The age of onset of the disease and smoking were significantly related with moderate or severe pneumoconiosis (OR 0.91, 95% CI 0.83-0.99; OR 6.94, 95% CI 1.54-31.30, respectively). However there was no significant difference between the rate of genetic polymorphism of GSTM1, GSTT1, GSTP1, CYP2E1 and CYP1A1 in the two groups.
CONCLUSION
NAT2 genetic polymorphism was higher in pneumoconiosis patients than in normal subjects. The age of onset of the disease and smoking were significantly related with pneumoconiosis. However, the genetic polymorphism of GSTM1, GSTT1, GSTP1, CYP2E1 and CYP1A1 was not related with development or severity of pneumoconiosis.

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Original Article

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers: Hyeon Woo Yim, Chung Yill Park, Young Man Roh, Kang Sook Lee, Jung Min Lee, Won Chul Lee, Se Hoon Lee, Chee Kyung Chung; Korean Journal of Occupational and Environmental Medicine 2000;12(3):405-420. Published online September 30, 2000; DOI: https://doi.org/10.35371/kjoem.2000.12.3.405

Abstract PDF

OBJECTIVES
The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism.
METHODS
The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood.
RESULTS
The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant.
CONCLUSIONS
Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

Citations

Citations to this article as recorded by

Applications of CYP-450 expression for biomonitoring in environmental health
Ho-Sun Lee, Mihi Yang
Environmental Health and Preventive Medicine.2008; 13(2): 84. CrossRef
Past and Future Applications of CYP450-Genetic Polymorphisms for Biomonitoring of Environmental Toxicants
Bitna Yi, Ji-Yeon Yang, Mihi Yang
Journal of Environmental Science and Health, Part C.2007; 25(4): 353. CrossRef

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Original Article

CYP2E1 Genetic Polymorphism relating to Styrene Metabolism of Korean Workers: Chang Hee Lee, Jin Ho Chun, Jun Han Park, Dong Mug Kang, Dae Hwan Kim, Deog Hwan Moon, Chae Un Lee; Korean Journal of Occupational and Environmental Medicine 1999;11(2):161-173. Published online June 30, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.2.161

Abstract PDF: The goal of this study is to observe the associations between the metabolic phenotype by personal exposure and urinary metabolites and genetic polymorphism of CYP2E1 which is known to be related with styrene metabolism. To complete this study, the author executed a battery of tests on 46 workers who were working at laminating department of fiberglass- reinforced plastics (FRP) industry located in Pusan and Kyungnam area during April to June 1998. Those were - (1) personal exposure assessment with organic vapour monitor and gas chromatography. (2) measurement of urinary metabolites - mandelic acid (MA) and phenylglyoxylic acid (PGA) - with high performance liquid chromatography (HIPLC), (3) CYP2E1 genotying with PCR and restriction fragment length polymorphism (RFLP) using Dra I and Rsa I, and (4) questionnaire survey for some individual characteristics. Study subjects were composed of 32 men and 14 women, and whose average age was 39.4 years, average tenure was 7.7 years. Each concentration expressed by geometric mean(range) was as follows; air styrene 15.6(3.1-81.0) ppm, urinary MA 187.8(36.8-1007.2) mg/g creatinine, PGA 232.8(46.8-1075.7) mg/g creatinine. Correlation coefficients between air styrene were MA 0.54, PGA 0.37, MA+PGA 0.54 (p < 0.05). The relative frequency of CYP2E1 mutant allele was 45.7%(Dra I 43.5%, lIsa 1 37.0%), and homozygous mutant type (M/M) was not observed. The value of (geometric mean of (air styrene/urinary metabolites)) x 1000 according to genotype was significantly higher in mutant type than wild type (p<0.05), as in case of MA, mutant type 106.4 and wild type 84.4, and in case of MA+PGA, mutant type 84.4 and wild type 55.6. The value of air styeneTLV-TWA/urinary metabolitesBEI was used as a cut-off value of classifying phenotype. That is, the value of air styeneTLV-TWA/urinary MABEI >or= 0.063 and air styreneTLV-TWA/urinary MA+PGABEI >or= 0.048 was classified as poor metabolizer, and, the value of air styreneTLV-TWA/urinary MABEI~ < 0.063 and air styreneThV~A/urinary MA+PGABEI < 0.048 was classified as extensive metabolizer. As the result, the frequency of poor metabolizer was higher in mutant type than wild type with no statistical significance (p > 0.05), as in case of MA, mutant type 66.7% and wild type 48.0%, and in case of MA+PGA, mutant type 81.0% and wild type 56.0%. These results suggests that CYP2E1 mutant allele has a tendency toward the poor metabolizer. This study has several limitations as small sample size, and no considerations on work intensity, alcohol habit, obesity, etc which can affect styrene metabolism. However, this study is of value because this is first study to propose the fundamental data about associations between exposure level, biological monitoring, and CYP2E1 genetic polymorphism in Korean workers dealing with pure styrene. To improve accuracy of the study, that means, to applicate the result of this study on the personal risk assessment of styrene workers, larger sample size and consideration for confounders are needed.

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