Parkinson's disease, pesticides, and glutathione transferase polymorphisms

被引:240
作者
Menegon, A
Board, PG [1 ]
Blackburn, AC
Mellick, GD
Le Couteur, DG
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Mol Genet Grp, Canberra, ACT 2601, Australia
[2] Univ Sydney, Canberra Hosp, Canberra Clin Sch, Dept Pharmacol, Canberra, ACT, Australia
[3] Univ Sydney, Canberra Hosp, Canberra Clin Sch, Dept Med, Canberra, ACT, Australia
[4] Univ Queensland, Princess Alexandra Hosp, Dept Med, Woolloongabba, Qld, Australia
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0140-6736(98)03453-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Parkinson's disease is thought to be secondary to the presence of neurotoxins, and pesticides have been implicated as possible causative agents. Glutathione transferases (GST) metabolise xenobiotics, including pesticides. Therefore, we investigated the role of GST polymorphisms in the pathogenesis of idiopathic Parkinson's disease. Methods We genotyped by PCR polymorphisms in four GST classes (GSTM1, GSTT1, GSTP1, and GSTZ1) in 95 Parkinson's disease patients and 95 controls. We asked all patients for information about pesticide exposure. Findings The distribution of the GSTP1 genotypes differed significantly between patients and controls who had been exposed to pesticides (controls vs patients: AA 14 [54%] of 26 vs seven [18%] of 39; AB 11 [42%] of 26 vs 22 [56%] of 39; BE 1 [4%] of 26 vs six [15%] of 39; AC 0 vs four [10%] of 39, p=0.009). No association was found with any of the other GST polymorphisms. Pesticide exposure and a positive family history were risk factors for Parkinson's disease. Interpretation GSTP1-1, which is expressed in the blood-brain barrier, may influence response to neurotoxins and explain the susceptibility of some people to the parkinsonism-inducing effects of pesticides.
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页码:1344 / 1346
页数:3
相关论文
共 30 条
  • [1] AliOsman F, 1997, J BIOL CHEM, V272, P10004
  • [2] BIOSYNTHESIS AND BIOTRANSFORMATION OF GLUTATHIONE S-CONJUGATES TO TOXIC METABOLITES
    ANDERS, MW
    LASH, L
    DEKANT, W
    ELFARRA, AA
    DOHN, DR
    [J]. CRC CRITICAL REVIEWS IN TOXICOLOGY, 1988, 18 (04): : 311 - 341
  • [3] [Anonymous], ANN NEUROL S
  • [4] Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes
    Baez, S
    SeguraAguilar, J
    Widersten, M
    Johansson, AS
    Mannervik, B
    [J]. BIOCHEMICAL JOURNAL, 1997, 324 : 25 - 28
  • [5] Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson's disease
    Bandmann, O
    Vaughan, J
    Holmans, P
    Marsden, CD
    Wood, NW
    [J]. LANCET, 1997, 350 (9085) : 1136 - 1139
  • [6] Board PG, 1997, BIOCHEM J, V328, P929
  • [7] ISOLATION OF A CDNA CLONE AND LOCALIZATION OF THE HUMAN GLUTATHIONE S-TRANSFERASE 3-GENES TO CHROMOSOME BANDS 11Q13 AND 12Q13-14
    BOARD, PG
    WEBB, GC
    COGGAN, M
    [J]. ANNALS OF HUMAN GENETICS, 1989, 53 : 205 - 213
  • [8] BOCCHETTA A, 1986, LANCET, V2, P1163
  • [9] GLUTATHIONE-S-TRANSFERASE IN HUMAN BRAIN
    CARDER, PJ
    HUME, R
    FRYER, AA
    STRANGE, RC
    LAUDER, J
    BELL, JE
    [J]. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1990, 16 (04) : 293 - 303
  • [10] GLUTATHIONE-S-TRANSFERASE M1 AND T1 POLYMORPHISMS - SUSCEPTIBILITY TO COLON-CANCER AND AGE-OF-ONSET
    CHENEVIXTRENCH, G
    YOUNG, J
    COGGAN, M
    BOARD, P
    [J]. CARCINOGENESIS, 1995, 16 (07) : 1655 - 1657