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Association of NRH:Quinone Oxidoreductase 2 Gene Promoter Polymorphism With Higher Gene Expression and Increased Susceptibility to Parkinson's Disease

Departments of ¹ Pharmacology and ² Neurology, Baylor College of Medicine, Houston, Texas.

Address correspondence to Janet L. Stringer, MD, PhD, Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: janets{at}bcm.edu

The N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) gene encodes an enzyme that catalyzes activation of quinones. Blood DNA from 80 control individuals and 118 age-matched Parkinson's disease patients were analyzed for NQO2 gene promoter polymorphisms. The results revealed three allelic variants, designated I-29, I-16, and D. These results were confirmed in fibroblast cell lines. In patients with Parkinson's disease, there was a significant increase in the frequency of the D allele, but there was no difference in the frequency of the alleles in familial compared to sporadic Parkinson's disease. The D and I-16 promoters direct higher NQO2 gene expression that results in higher enzyme activity. Overexpression of NQO2 in the catecholaminergic neuroblastoma SH-SY5Y cells resulted in increased production of reactive oxygen species when exposed to exogenous dopamine. The results suggest that the association of the D promoter with Parkinson's disease may be due to an increase in expression of the NQO2 gene.

Key Words: NRH:quinone oxidoreductase 2—Promoter polymorphism—Parkinson's disease

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