The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil.
Carcinogenesis
; 28(1): 112-7, 2007 Jan.
Article
em En
| MEDLINE
| ID: mdl-16864595
Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, maté drinking, cachaça and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r2 of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r2 of 0.10; and a model combining both exposure and genotype information had a total r2 of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Hidrocarboneto de Aril Hidroxilases
/
Glucuronosiltransferase
/
Receptores de Hidrocarboneto Arílico
/
Citocromo P-450 CYP1A1
/
Citocromo P-450 CYP1A2
/
Glucuronatos
/
Glutationa Transferase
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do sul
/
Brasil
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido