title: Evaluation of glutathione S-transferase GSTM1 and GSTT1 polymorphisms and methylmercury metabolism in an exposed Amazon population.
abstract: Over the last decades, the presence of methylmercury (MeHg) in the Amazon region of Brazil and its adverse human health effects have given rise to much concern. The biotransformation of MeHg occurs mainly through glutathione (GSH) in the bile mediated by conjugation with glutathione S-transferases (GST). Epidemiological evidence has shown that genetic polymorphisms may affect the metabolism of MeHg. The aim of this study was to evaluate the association between GST polymorphisms, GSH, and Hg levels in blood (B-Hg) and in hair (H-Hg) of an Amazon population chronically exposed to the metal through fish consumption. Blood and hair samples were collected from 144 volunteers (71 men, 73 women). B-Hg and H-Hg levels were determined by inductively coupled plasma-mass spectrometry, and GSH levels were evaluated by a spectrophotometric method. GSTM1 and T1 genotyping evaluation were carried out by multiplex polymerase chain reaction (PCR). Mean levels of B-Hg and H-Hg were 37.7 ± 24.5 μg/L and 10.4 ± 7.4 μg/g, respectively; GSH concentrations ranged from 0.52 to 2.89 μM/ml of total blood. Distributions for GSTM1/T1, GSTM1/GSTT1*0, GSTM1*0/T1, and GSTM1*0/GSTT1*0 genotypes were 35.4, 22.2, 25.0, and 17.4%, respectively. GSTT1 genotype carriers presented lower levels of B-Hg and H-Hg when compared to other genotypes carriers. In addition, GSTM1*0/GSTT1*0 individuals presented higher Hg levels in blood and hair than subjects presenting any other genotypes. There appeared to be no evidence of an effect of polymorphisms on GSH levels. Therefore, our data suggest that GST polymorphisms may be associated with MeHg detoxification.
authors.affiliation: Department of Clinical, Toxicological and Bromatological Analyses, School of Phamaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Gustavo Rafael
authors.initials: GR
authors.lastname: Mazzaron Barcelos
authors.forename: Kátia Cristina
authors.initials: KC
authors.lastname: de Marco
authors.forename: Denise
authors.initials: D
authors.lastname: Grotto
authors.forename: Juliana
authors.initials: J
authors.lastname: Valentini
authors.forename: Solange Cristina
authors.initials: SC
authors.lastname: Garcia
authors.forename: Gilberto Úbila
authors.initials: GÚ
authors.lastname: Leite Braga
authors.forename: Fernando
authors.initials: F
authors.lastname: Barbosa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D004247:DNA / Q000235:genetics; D005260:Female; D005506:Food Contamination; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006197:Hair / Q000737:chemistry; D006801:Humans; D008297:Male; D008767:Methylmercury Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004247:DNA; D005982:Glutathione Transferase; D008767:Methylmercury Compounds; D014874:Water Pollutants, Chemical; C413545:glutathione S-transferase T1