Mitochondrial complex I polymorphism and cigarette smoking in Parkinson’s disease

Abstract

In recent years, genetic association studies have been the focus of research and debate.1 The presence of mitochondrial complex I (NADH-ubiquinone oxidoreductase) deficiency in PD and the demonstration that rotenone, a complex I inhibitor, selectively kills dopaminergic neurones suggest that variation in the genes encoding mitochondrial complex I may be associated with risk of PD.2 Whereas in vitro experiments implicate a major role for mitochondrial DNA mutations of complex I in PD, clinical studies suggest that such mutations probably are not significant in most patients with PD.3 A polymorphism in mitochondrial nuclear genome (C to T in exon 2 of NDUFV2 ) increases susceptibility to PD in a Japanese population.2 As this polymorphism results in a Ala29Val substitution leading to a structural change in the protein,2 the findings in that study could be of significance. Cigarette smoking is associated with decreased complex I activity4 and is inversely related to risk of PD.5 To test our hypothesis that there may a link between genetic variation of mitochondrial complex 1 and cigarette smoking, we examined the association of NDUFV2 polymorphism and risk of PD and the interaction of this polymorphism and cigarette smoking. Genomic DNA was extracted from 224 patients with PD seen at our Movement Disorder Clinic and from 223 controls similar in age, sex, and …