title: Glutathione S-transferase M1 and GST T1 genetic polymorphisms and Raynaud's phenomenon in French vinyl chloride monomer-exposed workers.
abstract: Occupational vinyl chloride monomer (VCM) exposure can induce Raynaud's phenomenon (RP). However, not all VCM workers developed RP, which suggests an underlying genetic susceptibility. Genetic polymorphisms of glutathione S-transferases (GSTs), involved in VCM metabolism, have been shown to influence certain VCM-related health effects. We have conducted a case-control study of 58 subjects with RP along with 247 subjects without RP, from a population of 305 French workers exposed or formerly exposed to VCM, to assess any association between GST M1 and GST T1 gene polymorphisms, either separately or in combination, and the presence of RP. None of the GST M1 or GST T1 genotypes were significantly associated with the presence of RP among studied VCM workers. A combination of positive genotypes for both GST M1 and GST T1 was significantly associated with RP presence, compared to the other combinations of genotypes (OR=2.1, 95% CI=1.1-3.8). OR adjusted for age, smoking status, alcohol consumption and history of treated hypertension did not reach significance (OR=2.0, 95% CI=0.9-5.2). None of the GST M1 and GST T1 genotypes seem to contribute separately to the presence of RP, suggesting that they are not, when taken alone, a major determinant of interindividual variability for VCM-induced PR. However, the combination of both positive GST M1 and GST T1 genotypes appears to contribute slightly to susceptibility to RP in VCM-exposed subjects. Nevertheless, our study-the first to examine the role of a genetic component in the occurrence of RP secondary to occupational exposure to a chemical-corroborates the previous considerations that interaction between the genetic constitution and environmental factors is of importance in determining the health-adverse effects of VCM exposure.
authors.affiliation: Institut de Médecine du Travail, Faculté de Médecine, UFR Médecine, Univ Clermont 1, 28 place Henri Dunant, 63001, Clermont-Ferrand, France. Luc.FONTANA@u-clermont1.fr.|Service de Médecine du travail et de pathologie professionnelle, CHU Clermont-Ferrand, 28 place Henri Dunant, 63001, Clermont-Ferrand Cedex, France. Luc.FONTANA@u-clermont1.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Fontana
authors.affiliation: INSERM U271, 151 cours Albert Thomas, 69424, Lyon Cedex 03, France.
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Marion
authors.affiliation: Service d'épidémiologie, économie de santé et prévention, CHU Clermont-Ferrand, Hôtel Dieu, boulevard Léon Malfreyt, 63000, Clermont-Ferrand, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ughetto
authors.affiliation: Faculté de Médecine, Institut de Médecine du Travail, Université d'Auvergne, 28 place Henri Dunant, 63001, Clermont-Ferrand Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Catilina
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005602:France; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D011928:Raynaud Disease / Q000139:chemically induced / Q000235:genetics*; D014752:Vinyl Chloride / Q000633:toxicity*; D044465:White People
chemical_list: D005982:Glutathione Transferase; D014752:Vinyl Chloride; C413545:glutathione S-transferase T1