title: Use of the CYP2E1 genotype and phenotype for the biological monitoring of occupational exposure to styrene.
abstract: The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. We studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7mg/m(3)) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyse different polymorphisms of enzyme CYP2E1 from buccal swab. We found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.
authors.affiliation: Faculty of Medicine, Legal and Forensic Medicine Division, Miguel Hernández University, Carretera Alicante-Valencia, km 87, 03550 San Juan, Spain. mjose.prieto@umh.es
authors.forename: M J
authors.initials: MJ
authors.lastname: Prieto-Castelló
authors.forename: A
authors.initials: A
authors.lastname: Cardona
authors.forename: D
authors.initials: D
authors.lastname: Marhuenda
authors.forename: J M
authors.initials: JM
authors.lastname: Roel
authors.forename: A
authors.initials: A
authors.lastname: Corno
mesh_terms: D000328:Adult; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006038:Glyoxylates / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D008333:Mandelic Acids / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D020058:Styrene / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D006038:Glyoxylates; D008333:Mandelic Acids; D012333:RNA, Messenger; C012482:phenylglyoxylic acid; D020058:Styrene; D019392:Cytochrome P-450 CYP2E1; C037938:mandelic acid