Neuroscience Letters 375 (2005) 178–180 No associations between Parkinson’s disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes Starlyn Okada a , Federico M. Farin a , Patricia Stapleton a , Hanna Viernes a , Sean D. Quigley a , Karen M. Powers a , Terri Smith-Weller a , Gary M. Franklin a,b , W.T. Longstreth b,c , Phillip D. Swanson b , Harvey Checkoway a,c,∗ a Department of Environmental and Occupational Health Sciences, University of Washington, Box 357234, Seattle, WA 98195-7234, USA b Department of Neurology, University of Washington, Box 357234, Seattle, WA 98195-7234, USA c Department of Epidemiology, University of Washington, Box 357234, Seattle, WA 98195-7234, USA Received 4 October 2004; received in revised form 2 November 2004; accepted 3 November 2004 Abstract Reactive oxygen species derived from dopamine metabolism can induce oxidative stress and thus may contribute to Parkinson’s disease (PD) pathogenesis. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) detoxify quinones and quinonoid compounds. We investigated associations of genetic polymorphisms of NQO1 (C609T) and NQO2 (I/D, 29 base pairs) with PD in a population-based case-control study of 190 idiopathic PD cases and 305 unrelated controls matched on age and sex. No associations were detected for either gene variant or for any allele combinations. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Parkinson’s disease; Quinone oxidoreductases; NQO1; NQO2; Genetic polymorphisms There is a large body of evidence supporting a significant role of oxidative stress resulting from the generation of reactive oxygen species (ROS) in PD pathogenesis [7]. Quinones derived from dopamine metabolism are a potentially im- portant source of ROS [1]. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) are integral flavoproteins responsible for the detoxification and metabolism of quinones and quinonoid compounds. NQO1 and NQO2 are phase II detoxification enzymes that protect against accumulation of neurotoxic quinonoid compounds due to their two-electron reducing enzymatic properties [3,9]. Since the functions of these two quinone oxidoreductases are similar, altered enzymatic activities of ∗ Corresponding author. Tel.: +1 206 543 2052; fax: +1 206 685 3990. E-mail address: checko@u.washington.edu (H. Checkoway). both proteins may lead to an additive effect on oxidative damage. NQO1, also referred to as DT-diaphorase, is a 274-amino acid protein that catalyzes a two-electron reduction of var- ious quinones including their respective quinonoid deriva- tives into stable hydroquinones. NQO1 is the dominant intracellular two-electron transfer quinone reductase. Lo- calized to chromosome 16q22, the human NQO1 gene has a single nucleotide polymorphism resulting in a C to T substitution at base pair 609 in exon 3 converting a pro- line to a serine at codon 187, where the T/T genotype has been associated with a lack of protein [8]. This polymor- phism is significantly less common in ethnic Caucasians than in Chinese or native North Americans [4]. An in- vestigation of the NQO1 C609T polymorphism and PD in a Japanese population found no significant association (odds ratio [OR] 1.3, 95% CI 0.9–1.9) [5]. In contrast, the T allele was associated with a significantly elevated 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.11.009