Influence of genetic polymorphisms of styrene-metabolizing enzymes on the levels of urinary biomarkers of styrene exposure

Carbonari, Damiano; Mansi, Antonella; Proietto, Anna Rita; Paci, Enrico; Bonanni, Rossana Claudia; Gherardi, Monica; Gatto, Maria Pia; Sisto, Renata; Tranfo, Giovanna

doi:10.1016/j.toxlet.2015.01.002

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…One study found that the heterozygous genotypes CYP2E1*5b and CYP2E1*6 result in significantly reduced excretion of MA and PGA. 38 This report was supported by another study which found that individuals with the CYP2E1*5b heterozygote allele had decreased excretion of EB/S metabolites in comparison to the wild type homozygote. 39 Between genders, women have higher CYP2B6 expression in the liver 40 ; CYP2B6 has been shown to be the most effective Cytochrome P450 form, which initiates the conversion of styrene to styrene-7,8-oxide.…”

Section: Discussionmentioning

confidence: 59%

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005–2006 and 2011–2012

Capella

Roland

Geldner

et al. 2019

Environmental Research

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Section: Discussionmentioning

confidence: 59%

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005–2006 and 2011–2012

Capella

Roland

Geldner

et al. 2019

Environmental Research

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“…These EPHX1 SNPs were also shown to have an important role in epigenetic changes and hematotoxicity in benzene-exposed Chinese workers (Xing et al 2013). A significantly reduced excretion of styrene metabolites (mandelic and phenylglyoxylic acids) in occupationally exposed individuals carrying the His allele in EPHX1 rs1051740 has recently been observed (Carbonari et al 2015). This study confirmed the previously suggested EPHX1 role in the styrene detoxification pathway and genetic susceptibility to DNA damage in exposed subjects (Vodicka et al 2001, Laffon et al 2003, Vodicka et al 2004, Costa et al 2012).…”

Section: Ephx1 Role In Human Diseasementioning

confidence: 99%

Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease

Václavíková

Hughes

Souček

2015

Gene

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Microsomal epoxide hydrolase (EPHX1) is an evolutionarily highly conserved biotransformation enzyme for converting epoxides to diols. Notably, the enzyme is able to either detoxify or bioactivate a wide range of substrates. Mutations and polymorphic variants in the EPHX1 gene have been associated with susceptibility to several human diseases including cancer. This review summarizes the key knowledge concerning EPHX1 gene and protein structure, expression pattern and regulation, and substrate specificity. The relevance of EPHX1 for human pathology is especially discussed.

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“…However, the activities of these enzymes carry genetic susceptibilities. Carbonari et al (25) reported that a lower excretion level of MA+ PGA was detected for exposed subjects carrying both the heterozygous alleles CYP2E1*5B and CYP2E1*6 in comparison to the wild-type homozygous; however, no difference in the urinary metabolites of styrene was observed for GSTM1 and GSTT1 genotypes. Ma et al (15) also reported that no significant difference in the excretion levels of urinary metabolites was observed between active and null types of GSTM1 and GSTT1 .…”

Section: Discussionmentioning

confidence: 98%

Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

Kim¹

2015

Toxicological Research

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The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1*5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism.

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Influence of genetic polymorphisms of styrene-metabolizing enzymes on the levels of urinary biomarkers of styrene exposure

Cited by 11 publications

References 31 publications

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005–2006 and 2011–2012

Ethylbenzene and styrene exposure in the United States based on urinary mandelic acid and phenylglyoxylic acid: NHANES 2005–2006 and 2011–2012

Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in human disease

Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

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