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

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.