LRRK2 P755L variant in sporadic Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder of unknown etiology with probable involvement of genetic-environmental factors. The majority of PD cases ( approximately 90-95%) are sporadic, while familial cases account for approximately 5-10% of PD. In a recent report, a heterozygous LRRK2 P755L mutation within LRRK2 exon 19 was found in 2% of Chinese sporadic PD patients and in 0% of normal controls or Caucasians, suggesting that the mutation is disease-associated with ethnic specificity. To further evaluate the role of LRRK2 P755L variant in sporadic PD, we performed direct sequencing of LRRK2 exon 19 in 501 Japanese sporadic PD patients ( male 249, female 252, aged 28-92 years, mean 65.0 years) and 583 controls of the Japanese general population as an extended association study. In this group, we found six patients (6/501 = 1.2%) and eight controls of the general population (8/583 = 1.6%) with a heterozygous P755L variant (P = 0.80, chi(2) = 0.064). No other variants were found in exon 19. Together with previous reports, our extended case-controlled study of large sample size suggests that LRRK2 P755L is a non-disease-associated polymorphism in PD patients.