title: Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.
abstract: Oxidative stress is widely thought to contribute significantly to the pathogenesis Parkinson's disease (PD). Given the role of glutathione S-transferases (GSTs) in the conjugation of electrophiles and protection against reactive oxygen species, genes encoding the GSTs have been considered candidates for association studies of PD. We tested for associations between genotypes of GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non-deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of 214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of Caucasian ethnicity. No significant associations with any of the GST genotypes were observed. However, there was a marginally significant difference in the distribution of GSTP1 104 genotypes between cases and controls (P=0.07), with an excess of Ile104Val heterozygotes found among cases (odds ratio (OR)=1.43; 95% Confidence Interval (CI): 0.98-2.08). This difference in the genotype distribution was strongest among smokers (OR for heterozygote=1.92; 95% CI: 1.12-3.29) versus non-smokers and among males (OR for heterozygote=1.99; 95% CI: 1.24-3.19) versus females. The distribution of GSTP1 Ile104Val and Ala113Val haplotypes did not differ between cases and controls. Taken together, these results suggest a potentially minor role of GSTP1 in PD, but do not give evidence for associations with either GSTM1 or GSTT1.
authors.affiliation: Department of Environmental Health, Box 357234, University of Washington, Seattle 98195-7234, USA.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Kelada
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Stapleton
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.forename: David L
authors.initials: DL
authors.lastname: Eaton
authors.forename: Terri
authors.initials: T
authors.lastname: Smith-Weller
authors.forename: Gary M
authors.initials: GM
authors.lastname: Franklin
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Swanson
authors.forename: W T
authors.initials: WT
authors.lastname: Longstreth
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology*; D011110:Polymorphism, Genetic
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human