GENOTYPE IN THE 24-KDA SUBUNIT GENE (NDUFV2) OF MITOCHONDRIAL COMPLEX-I AND SUSCEPTIBILITY TO PARKINSON-DISEASE

We analyzed the gene encoding the 24-kDa subunit of mitochondrial comp lex I, which has been implicated in the pathogenesis of Parkinson dise ase (PD). We set out to identify a polymorphism in the 24-kDa subunit gene (NDUFV2) in patients with PD and determine whether genetic polymo rphism of this gene is associated with a higher risk of PD. The subjec ts comprised 126 patients with PD, and the control group comprised 113 unrelated individuals without neurodegenerative disorders. A novel po lymorphism (Ala29Val) in the mitochondrial targeting sequence of NDUFV 2 was found in patients with PD. The distribution of the three genotyp es was significantly different between the two groups (chi(2) = 7.53, df = 2, P = 0.023). The frequency of homozygotes for the mutation was significantly higher in PD patients (23.8%) than in control subjects ( 11.5%, Fisher's exact test, P = 0.0099 < 0.01). The risk of developing PD associated with homozygosity for this mutation was calculated as 2 .40 (95% CI: 1.18-4.88). NDUFV2 constitutes one genetic risk factor fo r PD, and the mutation may well be a cause of complex I deficiency in this disease. (C) 1998 Academic Press.