CYP2E1 Genetic Polymorphism relating to Styrene Metabolism of Korean Workers

Lee, Chang Hee; Chun, Jin Ho; Park, Jun Han; Kang, Dong Mug; Kim, Dae Hwan; Moon, Deog Hwan; Lee, Chae Un

Abstract

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.