An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2.
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.
Harada
S
S
Institute of Community Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan. sjharada@md.tsukuba.ac.jp
Fujii
C
C
Hayashi
A
A
Ohkoshi
N
N
D000368:Aged; D000483:Alleles; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011336:Probability; D011401:Promoter Regions, Genetic / Q000235:genetics; D011808:Quinone Reductases / Q000235:genetics* / Q000378:metabolism
D005982:Glutathione Transferase; D011808:Quinone Reductases; C041831:NADH dehydrogenase (quinone); C419642:NRH - quinone oxidoreductase2