Association of NRH:quinone oxidoreductase 2 gene promoter polymorphism with higher gene expression and increased susceptibility to Parkinson's disease

Wei Wang, Weidong Le, Tianhong Pan, Janet L. Stringer, Anil K. Jaiswal

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume63
Issue number2
DOIs
StatePublished - Feb 2008

Keywords

  • NRH:quinone oxidoreductase 2
  • Parkinson's disease
  • Promoter polymorphism

ASJC Scopus subject areas

  • Aging

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