Mitochondrial Complex I Gene Variant Associated With Early Age at Onset in Spinocerebellar Ataxia Type 2

Background A common mitochondrial complex I gene polymorphism (10398G) is reported to be inversely associated with the risk of Parkinson disease. We hypothesized that this variant might have a protective effect on the central nervous system and therefore might delay the onset of symptoms in spinocerebellar ataxia type 2 (SCA2). Objective To assess the association of the 10398G polymorphism with age at onset in Cuban patients with SCA2. Design Genetic association study. Setting Holguin, Cuba. Patients Forty-six Cuban patients with SCA2. Main Outcome Measures Presence or absence of the 10398G polymorphism was determined in 46 Cuban patients with SCA2 and early or late onset of symptoms, defined as at least 2 SDs lower than or higher than the mean age at onset for patients with a similarly sized triplet repeat expansion. Results The polymorphism was present in 11 of 27 Cuban patients with SCA2 and early onset (41%) vs 2 of 19 with late onset (11%) (Fisher exact test; P = .04). Conclusion Contrary to our prediction of a later onset of SCA2 in patients with the 10398G polymorphism, we find that this variant is associated with an earlier age at onset in Cuban patients with SCA2.