LRRK2 P755L variant in sporadic Parkinson's disease

Abstract

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, χ2 = 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. © 2008 The Japan Society of Human Genetics and Springer.