Annals of Occupational and Environmental Medicine

Research Article

Association between prenatal polycyclic aromatic hydrocarbons and infantile allergic diseases modified by maternal glutathione S-transferase polymorphisms: results from the MOCEH birth cohort: Tai Kyung Koh, Hyesook Park, Yun-Chul Hong, Mina Ha, Yangho Kim, Bo-Eun Lee, Surabhi Shah, Eunhee Ha; Ann Occup Environ Med 2021;33:e12. Published online April 23, 2021; DOI: https://doi.org/10.35371/aoem.2021.33.e12

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Background

Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study.

Methods

The study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed.

Results

The risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP μg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP μg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant.

Conclusions

The present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Citations

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Infantile allergic diseases: a cohort study prenatal fish intake and mercury exposure context
Surabhi Shah, Hae Soon Kim, Yun-Chul Hong, Hyesook Park, Mina Ha, Yangho Kim, Ji Hyen Lee, Eun-Hee Ha
BMC Public Health.2024;[Epub] CrossRef
Prenatal dietary exposure to mixtures of chemicals is associated with allergy or respiratory diseases in children in the ELFE nationwide cohort
Manel Ghozal, Manik Kadawathagedara, Rosalie Delvert, Amandine Divaret-Chauveau, Chantal Raherison, Raphaëlle Varraso, Annabelle Bédard, Amélie Crépet, Véronique Sirot, Marie Aline Charles, Karine Adel-Patient, Blandine de Lauzon-Guillain
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Prenatal dietary exposure to chemicals and allergy or respiratory diseases in children in the EDEN mother–child cohort
Manel Ghozal, Manik Kadawathagedara, Rosalie Delvert, Karine Adel-Patient, Muriel Tafflet, Isabella Annesi-Maesano, Amélie Crépet, Véronique Sirot, Marie Aline Charles, Barbara Heude, Blandine de Lauzon-Guillain
Environment International.2023; 180: 108195. CrossRef
Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review
Sumitaka Kobayashi, Fumihiro Sata, Reiko Kishi
Environmental Health and Preventive Medicine.2022; 27: 24. CrossRef
Role of GSTM1 in Hypertension, CKD, and Related Diseases across the Life Span
Rebecca Levy, Thu H. Le
Kidney360.2022; 3(12): 2153. CrossRef

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Review

Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure: Jung Ran Choi, Seong Yong Park, O Kyu Noh, Young Wha Koh, Dae Ryong Kang; Ann Occup Environ Med 2016;28:13. Published online March 16, 2016; DOI: https://doi.org/10.1186/s40557-016-0095-2

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Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in worldwide. The cumulative survival rate at five years differs between 13 and 21 % in several countries. Although the most important risk factors are smoking for lung cancer, however, the increased incidence of lung cancer in never smokers(LCINS) is necessary to improve knowledge concerning other risk factors. Environmental factors and genetic susceptibility are also thought to contribute to lung cancer risk. Patients with lung adenocarcinoma who have never smoking frequently contain mutation within tyrosine kinase domain of the epidermal growth factor receptor(EGFR) gene. Also, K-ras mutations are more common in individuals with a history of smoking use and are related with resistance to EFGR-tyrosine kinase inhibitors. Recently, radon(Rn), natural and noble gas, has been recognized as second common reason of lung cancer. In this review, we aim to know whether residential radon is associated with an increased risk for developing lung cancer and regulated by several genetic polymorphisms.

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Janak L. Pathak, Yongyong Yan, Qingbin Zhang, Liping Wang, Linhu Ge
Respiratory Medicine.2021; 185: 106475. CrossRef
Analysis of human papillomaviruses and human polyomaviruses in lung cancer from Swedish never-smokers
Torbjörn Ramqvist, Christian Ortiz-Villalon, Eva Brandén, Hirsh Koyi, Luigi de Petris, Gunnar Wagenius, Ola Brodin, Christel Reuterswärd, Tina Dalianis, Mats Jönsson, Johan Staaf, Rolf Lewensohn, Maria Planck
Acta Oncologica.2020; 59(1): 28. CrossRef
Gene polymorphism of DNA repair gene X‐ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non‐small‐cell lung cancer for Chinese nonsmoking female patients
Lei Wang, Le‐Le Wang, Di Shang, Sheng‐Jie Yin, Li‐Li Sun, Xiao‐Ying Wang, Hong‐Bo Ji
The Kaohsiung Journal of Medical Sciences.2019; 35(1): 39. CrossRef
Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from bronchial epithelial cell line induced by α-particles radiation
Qiaowei Liu, Hao Li, Lukuan You, Tao Li, Lingling Li, Pingkun Zhou, Xiaochen Bo, Hebing Chen, Xiaohua Chen, Yi Hu, Christophe Antoniewski
PLOS ONE.2019; 14(6): e0213047. CrossRef
Non-Smoking-Associated Lung Cancer: A distinct Entity in Terms of Tumor Biology, Patient Characteristics and Impact of Hereditary Cancer Predisposition
Elisabeth Smolle, Martin Pichler
Cancers.2019; 11(2): 204. CrossRef
Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma
Sun Min Lim, Jae Woo Choi, Min Hee Hong, Dongmin Jung, Chang Young Lee, Seong Yong Park, Hyo Sup Shim, Seungsoo Sheen, Kyeong Im Kwak, Dae Ryong Kang, Byoung Chul Cho, Hye Ryun Kim
Lung Cancer.2019; 131: 139. CrossRef
Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers
Junjie Yang, Xiaofeng Mu, Ye Wang, Dequan Zhu, Jiaming Zhang, Cheng Liang, Bin Chen, Jingwen Wang, Changying Zhao, Zhiwen Zuo, Xueyuan Heng, Chunling Zhang, Lei Zhang
Frontiers in Oncology.2018;[Epub] CrossRef
Radon and Lung Cancer: Disease Burden and High-risk Populations in Korea
Young Woo Jin, Songwon Seo
Journal of Korean Medical Science.2018;[Epub] CrossRef
Radon Exposure-induced Genetic Variations in Lung Cancers among Never Smokers
Jung Ran Choi, Sang Baek Koh, Hye Ryun Kim, Hyojin Lee, Dae Ryong Kang
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Journal of Cancer Prevention.2017; 22(4): 234. CrossRef

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Original Article

The Association among Exposure of Bisphenol A, Genetic Polymorphism of Metabolic Enzyme and Urinary Metabolite: Sang Baek Koh, Jun Ho Park, Su Song Yun, Sung Su Oh, Sei Jin Chang, Sun Haeng Choi, Bong Suk Cha; Korean Journal of Occupational and Environmental Medicine 2008;20(2):112-118. Published online June 30, 2008; DOI: https://doi.org/10.35371/kjoem.2008.20.2.112

Abstract PDF

OBJECTIVES
To examine bisphenol A (BPA) exposure with subjects in the manufacturing industry and to determine its correlation with metabolites according to genetic polymorphism of metabolic enzymes.
METHODS
The study subjects comprised 104 workers in the manufacturing industry, 64 and 40 in the exposed and control groups, respectively. The questionnaire variablesincluded age, use of protective equipment, smoking habit and alcohol intake. Their urine samples were collected in the afternoon and urinary BPA concentration was measured by revising with the urinary creatinine concentration. The genetic polymorphism of the metabolic enzymes was examined by using restriction fragment length polymorphism (RFLP) after extracting DNA from leucocytes.
RESULTS
The minimum and maximum BPA level of the exposed group during working time was 34.22 and 221.20 ng/mg, respectively. The urinary BPA concentration was significantly higher in the exposed groups than in the control group. There was no significant difference in the urinary BPA level according to genetic polymorphism of CYP1A1 and CYP2E1, but UGT1A6 showed a significant difference. In multiple regression analysis on the urinary and airborne BPA levels, UGT1A6, use of protective equipments and workplaces were significant variables.
CONCLUSIONS
The urinary BPA concentration was affected by the levels to which workers were exposed during their working time and was considered to be metabolized by UGT1A6.

Citations

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Filling gaps between exposure modeling and the analysis of urinary biomarkers using personal air monitoring: An intervention study of permethrin used in home insecticide spray
Seon‐Kyung Park, Heon‐Jun Lee, Eugene Song, Yerin Jung, Hyun Jung Yoo, Jeong‐Eun Oh, Hyeong‐Moo Shin, Jung‐Hwan Kwon
Indoor Air.2022;[Epub] CrossRef
Study Design, Rationale and Procedures for Human Biomonitoring of Hazardous Chemicals from Foods and Cooking in Korea
Seokwon Lee, Ryoung Me Ahn, Jae Hyoun Kim, Yoon-Deok Han, Jin Heon Lee, Bu-Soon Son, Kyoungho Lee
International Journal of Environmental Research and Public Health.2019; 16(14): 2583. CrossRef

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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 Effect of ALAD and VDR Polymorphism on the Hematopoietic Biomarkers in Lead Exposed Workers: Sung Soo Lee, Nam Soo Kim, Jin Ho Kim, Yong Bae Kim, Young Hwangbo, Hwa Sung Kim, Kyu Dong Ahn, Byung Kook Lee; Korean Journal of Occupational and Environmental Medicine 2005;17(4):343-351. Published online December 31, 2005; DOI: https://doi.org/10.35371/kjoem.2005.17.4.343

Abstract PDF: OBJECTIVES
This study was conducted with new workers who entered lead industries from 1992 to 2001 to evaluate the genetic susceptibility of ALAD (delta-aminolevulinic acid dehydratase) and VDR (vitamin D receptor) gene on health effect of lead exposure.
METHODS
Among the subjects of the database of lead industries at the Soonchunhyang University Institute of Industrial Medicine, only new workers were selected for this study. The total of eligible workers for this category was 3,540 workers, including non lead exposed workers of same lead industries. From stored blood in specimen bank of Soonchunhyang University, genotype of ALAD and VDR were measured using PCR method. Variables for this study were blood lead as an index of lead exposure, ZPP (zinc protoporphyrin in blood), urine ALA (delta-aminolevulinic acid), and hemoglobin as an index of hematopoietic effect of lead. Information on sex, job duration, and weight were collected for personal information. The data were analyzed using SAS (version 8.2) with descriptive analysis of t-test and multiple regression analysis.
RESULTS
Among 3,540 new employed study subjects during period of 1992-2001, 3,204 workers (90.5%) had ALAD genotype 1-1, while 336 workers (9.5%) had variant type of ALAD (1-2 or 2-2). For VDR genotype, 2,903 workers (89.7%) out of total tested 3,238 workers were belonged to type bb and 335 workers (10.5%) were type bB or BB. The distribution of genotype of ALAD and VDR were not different according to the job duration in male workers, but were different in female workers. The effect of ALAD and VDR genotype on blood lead were positively significant in the analysis of all cumulative data of new employed workers for 10 years. The effect of VDR genotype on blood lead were stronger than that of ALAD. While the variant ALAD gene made decrease of mean ZPP and ALA in urine after controlling for blood lead and other covariate, the variant VDR gene made increased the mean ZPP and ALA in urine in all cumulative data analysis and cross sectional analysis by job duration. For hemoglobin, ALAD and VDR genotype did not affect the mean value.
CONCLUSIONS
From the above our results, we found that ALAD and VDR genotype exerted significant effect in various way. We confirmed that the finding of a cross sectional study of protective effect of variant ALAD on the effect of blood lead on blood ZPP in our retrospective study design. It was found that VDR did not exert protective effect for lead exposure as the variant ALAD did.

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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

Associations of ALAD Genotype with Renal Function Indices in Lead Workers: Sung Soo Lee, Jin Ho Kim, Nam Soo Kim, Hwa Sung Kim, Kyu Dong Ahn, Byung Kook Lee; Korean Journal of Occupational and Environmental Medicine 2004;16(2):200-209. Published online June 30, 2004; DOI: https://doi.org/10.35371/kjoem.2004.16.2.200

Abstract PDF

OBJECTIVES
delta-Aminolevulinic acid dehydratase (ALAD) is a polymorphic enzyme that has two alleles, ALAD1 (ALAD1-1 as genotype) and ALAD2 (ALAD1-2 or ALAD2-2 as genotype). ALAD genotype has been reported to modify the pharmacokinetics and toxicity of lead. The authors investigated the influence of ALAD genotype polymorphism on renal function in lead workers METHODS: We studied 935 male lead workers and 87 male non-lead workers in the same industries. For cross-sectional renal indices, blood urea nitrogen (BUN), serum creatinine, serum uric acid and urine total protein were selected. Blood lead level was also measured an index of lead exposure. Information on weight, age, job duration, and smoking and drinking habits was collected.
RESULTS
Whereas the mean blood lead level of lead workers was 25.4+/-10.9 microgram/dL, that of non-lead workers in the same premise was 10.1+/-2.8 microgram/dL, and the difference between the two groups was statistically significant. Whereas the prevalence of the variant allele, ALAD2 in 935 lead workers was 10.6%, that in 87 non-lead workers was 4.6%. However there was no difference of prevalence between the two groups. The mean blood lead level of subjects with ALAD1 was 23.9+/-11.4 microgram/dL, which was slightly lower than that of subjects with ALAD2 (25.8+/-10.7 microgram/dL). However, this difference was not statistically significant. After adjustment for the covariates, the subjects with ALAD2 allele were 12.8% less likely to have a median value or more of BUN than subject with ALAD1. The adjusted odds ratio was 0.59 (95% confidence interval; 0.38-0.91). After adjustment for the covariates, the subjects with ALAD2 allele were 9.3% less likely to have a median value or more of serum creatinine than subject with ALAD1. The adjusted odds ratio was 0.64 (95% confidence interval; 0.41-0.98).
CONCLUSIONS
From the above results, it was found that the variant allele, ALAD2 appeared to modify the association of lead and renal function, and that ALAD2 genotype may be supportive for the protective effect of lead.

Citations

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Effects of Factors Associated with Urine Hippuric Acid Correction Values in Urinary Creatinine by HPLC and Jaffe Method and Specific Gravity HPLC Jaffe Method
Key-Young Kim, Jong-Gyu Kim, Ki-Nam Yoon, Wha-Me Park, Hun-Hee Park
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(4): 493. CrossRef
Environmental Exposure to Lead (Pb) and Variations in Its Susceptibility
Jina Kim, Youngeun Lee, Mihi Yang
Journal of Environmental Science and Health, Part C.2014; 32(2): 159. CrossRef

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Original Article

The Role of TNFalpha Gene Promoter Polymorphism in the Development of Coal Workers' Pneumoconiosis: Byoung Yong Ahn, Kyoung Ah Kim, Hae Yun Nam, Je Hyeok Mun, Jin Sook Jeoung, Young Lim; Korean Journal of Occupational and Environmental Medicine 2002;14(2):117-123. Published online June 30, 2002; DOI: https://doi.org/10.35371/kjoem.2002.14.2.117

Abstract PDF: OBJECTIVES
This study was performed in order to investigate the frequency of the TNF2 allele in patients with coal workers pneumoconiosis (CWP).
METHODS
We compared the genotype distribution of TNFalpha gene promoter polymorphism between 80 CWP patients and 54 healthy controls.
RESULTS
The results were as follows : 1. The rare allele TNF2 was significantly more frequent in CWP patients (20.6 %) than in controls (10.2 %). 2. The spontaneous or LPS-induced release of TNFalpha from the peripheral monocytes was slightly increased in the TNF2 group, but these values were not significantly different between groups. 3. In the CWP TNF2 group, the increase of LPS-induced TNFalpha release was significant in comparison with that of the controls.
CONCLUSIONS
From the above results, we suggest that the TNF2 allele is strongly associated with susceptibility to CWP development.

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Original Article

The Effect of ALAD Polymorphism on the Relationship of Blood and Bone Lead with Hematologic Biomarkers in Lead Exposed Workers: Hwa Sung Kim, Sung Soo Lee, Yong Bae Kim, Young Hwangbo, Gap Soo Lee, Kyu Dong Ahn, Bong Ki Jang, Byung Kook Lee; Korean Journal of Occupational and Environmental Medicine 2001;13(1):75-86. Published online March 31, 2001; DOI: https://doi.org/10.35371/kjoem.2001.13.1.75

Abstract PDF: OBJECTIVES
To evaluate the effect of ALAD polymorphism on the relationship of blood and bone lead with hematologic biomarkers in lead exposed workers, 450 lead exposed workers and 85 non-lead exposed workers were selected.
METHODS
Blood lead and tibia bone lead were selected as parameters of lead exposure and blood ZPP, urinary ALA (ALAU), hemoglobin (Hb) and hematocrit (Hct) were chosen as parameters of hematologic effect of lead exposure. Genotype of each subject was assayed and expressed as ALAD1 and ALAD2. Demographic information such as sex, age and personal habit of smoking and drinking were collected. Job duration of lead exposed workers was also obtained.
RESULTS
The overall prevalence of the variant allele, ALAD2 in lead exposed workers was 9.6 %(43 out of 450 lead workers) which was not differed from control workers (9.4 % : 8 out of 85). The means of tibial lead and blood ZPP in lead workers with ALAD2 were lower than those of lead workers with ALAD1, but the differences were not statistically significant. After adjusting for possible confounders (sex, job duration, BMI, drinking and smoking status) only blood lead and bone lead contributed negatively to the level of hemoglobin with statistical significance without any contribution of ALAD genotype. On the other hand, no significant effect of blood lead, bone lead and ALAD genotype were observed on the level of hematocrit after controlling possible confounder. ALAD genotype in the multiple regression analysis of blood lead and bone lead with log transformed urinary ALA (LogALAU) after adjusting for possible confounders showed significant main and interaction effect on LogALAU simultaneously, which resulted lower LogALAU in lead exposed workers of ALAD2 than ALAD1. It was also observed only main effect of ALAD gene type on blood ZPP after adjusting possible confounder resulting lower ZPP in lead workers of ALAD2 than ALAD1.
CONCLUSIONS
With above results, it was found that ALAD polymorphism did not affect on the level of hemoglobin and hematocrit, but ALAD polymorphism made significant effect on the association of blood and bone lead with urinary ALA and blood ZPP. The lower urinary ALA and blood ZPP in ALAD2 lead workers suggested that ALAD2 genotype may be supportive for the protective effect of lead.

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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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Original Article

A Meta-analysis on the Association between Bladder Cancer and Glutathione S transferase mu Genetic Polymorphism: Sang Baek Koh, Bong Suk Cha, Jong Ku Park, Chun Bae Kim, Myung Gun Kang, Ki Woong Kim, Won Jin Lee, Soung Hoon Chang; Korean Journal of Occupational and Environmental Medicine 1999;11(1):13-23. Published online March 31, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.1.13

Abstract PDF: This study was conducted to integrate the results of studies which assess the relationship between bladder cancer and Glutathione S transferase mu genetic polymorphism. We retrieved the literatures using MEDLINE search, with bladder cancer and Glutathione S transferase as key words, which were reported from 1980 to October 1998. The criteria for quality evaluation were as follows; 1) The paper should have histologically confirmed bladder cancer as case definition. 2) The paper should use the GSTM1 gene typing as method for analysis. Among 59 retrieved articles, fourteen studies were selected for quantitative meta-analysis. The overall effect size of the risk of bladder cancer due to GSTM1 was calculated by common odds ratio. Before the integration of each effect sizes into common effect sizes, the homogeneity test were conducted. All studies were case control design and cases were transitional cell carcinoma or squamous cell carcinoma of bladder. And only four papers used matching technique. Homogeneity of studies were rejected by Breslow-Day test(P<0.01), so random effect model was used for evaluation of odds ratio. The overall odds ratio of GSTM1 associated with bladder cancer was 1.55 (95% confidence interval 1.27 to 1.90) and cumulative odds ratio became more stable when the study subjects were over 1,500. Our result suggested that positive association be found between GSTM1 genetic polymorphism and bladder cancer.

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Original Article

ALDH2 Genetic Polymorphism and Urinary Hippuric Acid Concentration in Toluene Exposed Workers: Oh Choon Kwon, Ree Joo, Jung Jeung Lee, Chang Yoon Kim, Jong Hak Chung, Seong Yong Kim; Korean Journal of Occupational and Environmental Medicine 1997;9(2):332-340. Published online June 30, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.2.332

Abstract PDF: In this study we evaluated the effects of the genetic polymorphism of aldehyde dehydrogenase2 (ALDH2) on toluene metabolism and determined biological exposure indices (BEIs) for toluene by the genotypes of ALDH2. The study subject were 77 men workers who are handling toluene in a video tape manufacturing factory and a textile company. Through the face-to-face interview, the information about smoking and drinking behavior wag obtained. For determination of ALDH2 poly morphism, 5 ml of venous blood sample was obtained from each subject after informed consent. DNA was extracted from the buffy coat and ALDH2 genotyping were performed using a polymerase chain reaction (PCR) method. The genotype of ALDH2 was classified into the homozygous genotype of normal ALDH2 (NN), and the heterozygous genotype of normal and inactive ALDH2 (ND), and homozygous genotype of an inactive ALDH2(DD). The concentration of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens collected at the end of shift, corrected with creatinine (HA/C), and compared with BEI for toluene, which is 2.5 g/g creatinine. The personal exposure level of toluene were monitored, using personal air sampler and analyzed by gas chromatography. The frequencies of the three genotypes in this study subjects were, NN : 45 (58.4%), ND : 26 (33.8%) and DD : 6 (7.8%), and frequencies of the genotypes in the middle or heavy toluene exposure workers were not significantly different from those in the mild toluene exposure workers. The frequencies of the DD type of ALDH2 was lower among alcohol drinkers than among non-drinkers. The urinary HA concentration of DD group was significantly lower than that of the NN or ND group, which suggests that the HA formation from toluene decreased in DD group. Regression lines were used to estimate the BEIs of the NN, ND, and DD groups. NN : y = 0.0085x + 0.23, r = 0.90 ND : y = 0.0074x + 0.21, r = 0.85 DD : y = 0.0041x + 0.82, r = 0.83 The three regression lines revealed that the estimated urinary HA concentration of NN, ND, and DD groups at 377 mg/m3 toluene(TLV-TWA) exposure were 3.43, 3.00, and 2.37 g/g creatinine, respectively. The HA concentration of the NN, and ND group were higher than that of the ACGIH BEI (2.5 g/g creatinine) ; however, the HA level of DD group was lower than the BEI. These results suggests that the ACGIH BEI is not adequate to estimate the toluene exposure of the NN, ND and DD groups at the same time. Based upon those results, a new BEI for ALDH2 deficient workers may be necessary.

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