Mitochondrial translation initiation factor 3 polymorphism and Parkinson's disease

Mitochondrial dysfunction has been proposed to play a role in the pathogenesis of Parkinson's disease (PD). Supportive of this hypothesis, several genetic variants that regulate mitochondrial function and homeostasis have been described to alter PD susceptibility. A recent report demonstrated association of a single nucleotide polymorphism in the mitochondrial translation initiation factor 3 (MTIF3) gene with PD risk. The protein encoded by this nuclear gene is essential for initiation complex formation on the mitochondrial 55S ribosome and regulates translation of proteins within the mitochondria. Changes in the function or expression of the MTIF3 protein may result in altered mitochondrial function, ATP production or formation of reactive oxygen species thereby affecting susceptibility to PD. We examined the association of rs7669 with sporadic PD in three Caucasian case control series (n= 2434). A significant association was observed in the largest series (Norwegian; n= 1650) when comparing CC vs. CT/TT genotypes, with the Irish and US series having a similar but non-significant trend. The combined series also revealed an association with risk of PD (P= 0.01), supporting the possible involvement of this gene in PD etiology.