An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2.

Abstract

Individual vulnerability to reactive intermediates and oxidative stress accompanying metabolism of endogenous toxic compounds in the brain may promote the development of PD. Phase II detoxification enzymes such as glutathione S-transferase M1 (GSTM1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH):quinone oxidoreductase 2 (NQO2) are important as cellular defenses against catecholamine-derived quinones and the oxidative stress that arises as a consequence of their metabolism. We conducted a study of the potential association between idiopathic Parkinson's disease and polymorphisms of GSTM1, NQO1, and NQO2. DNA samples from 111 unrelated outpatients with idiopathic PD and 100 unrelated healthy volunteers were analyzed. GSTM1 deletion polymorphism exhibited no positive association with PD (P = 0.596, odds ratio: 1.135), although GSTM1 were grouped into three genotypes (deletion/deletion, deletion/nondeletion, and nondeletion/nondeletion). In addition, polymorphism of the NQO1 gene caused by a C to T substitution in exon 3 presented no association with PD (P = 0.194, odds ratio: 1.31). However, polymorphism in the form of an insertion/deletion (I/D) of 29 base pairs (bp) nucleotides in the promoter region of the NQO2 gene, which contains four repeats of the putative core sequence (GGGCGGG) of the Sp1-binding cis-element, did associate with PD. The frequency of the D allele was significantly higher in patients with PD than in controls (P < 0.0001, odds ratio: 3.463). Our data suggested that the deletion of 29-bp nucleotides in the promoter region of the NQO2 gene associates with the development of PD.

• Authors: S Harada, C Fujii, A Hayashi, N Ohkoshi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 288 Issue 4 Pg. 887-92 (Nov 09 2001) ISSN: 0006-291X [Print] United States
• PMID: 11688992 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• NADH dehydrogenase (quinone)
• NRH - quinone oxidoreductase2
• Quinone Reductases
• Glutathione Transferase
• glutathione S-transferase M1

Topics

• Aged
• Alleles
• Exons (genetics)
• Female
• Gene Frequency (genetics)
• Genotype
• Glutathione Transferase (genetics, metabolism)
• Humans
• Introns (genetics)
• Male
• Parkinson Disease (enzymology, genetics)
• Polymorphism, Genetic (genetics)
• Probability
• Promoter Regions, Genetic (genetics)
• Quinone Reductases (genetics, metabolism)