The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers.
Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such knowledge could benefit us in understanding the inter-individual difference in the mechanism of PAHs-induced carcinogenesis. We investigated the influence of gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from two coking plants in south China. After adjustment for age, plant, level of occupational exposure, body mass index, level of education, alcohol consumption, cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 -3263T>G (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of urinary 1-OHP (Geometric mean, micromol/mol creatinine) in the homozygous major variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 -3263T>G and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92, 4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA carriers (5.17 vs. 3.64 micromol/mol creatinine, p=0.038), as well as in the case with UGT1A1 -3263T>G TG/GG carriers (5.67 vs. 3.38 micromol/mol creatinine, p=0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms were associated with urinary 1-OHP concentrations in Chinese coke oven workers. No influence was found in the association between urinary 1-OHP and other genetic polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this population.
Chen
Bo
B
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, 200032, PR China.
Hu
Yunping
Y
Jin
Taiyi
T
Lu
Daru
D
Shao
Minhua
M
Zheng
Lixing
L
Wang
Qiangyi
Q
Shen
Yue
Y
Liu
Hongliang
H
Liu
Yanhong
Y
Zhou
Yuanfen
Y
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers / Q000652:urine; D002681:China; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D009153:Mutagens / Q000032:analysis*; D016273:Occupational Exposure / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000032:analysis*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D000099148:UGT1A1 Enzyme
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D014453:Glucuronosyltransferase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D009153:Mutagens; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D018336:Receptors, Aryl Hydrocarbon; D000099148:UGT1A1 Enzyme; C111235:AHR protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C033146:1-hydroxypyrene