A Study on Polymorphism Affecting Excretion of Urinary Methylhippuric Acid due to Xylene Exposure.

Objectives: The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism.

Methods: Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood.

Results: 1. The urinary concentrations of o-, m-, and pmethylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p< 0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p< 0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p> 0.05).

Conclusions: Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed.