A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan

Alessio Di Fonzo, Yah Huei Wu-Chou, Chin Song Lu, Marina Van Doeselaar, Erik J. Simons, Christan F. Rohé, Hsiu Chen Chang, Rou Shayn Chen, Yi Hsin Weng, Nicola Vanacore, Guido J. Breedveld, Ben A. Oostra, Vincenzo Bonifati

Research output: Contribution to journalArticlepeer-review


Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic forms of PD remains largely unknown. Data are particularly limited concerning the Asian population. In search for novel, biologically relevant variants, we sequenced the LRRK2 coding region in Taiwanese patients with PD. Four newly identified variants and another variant recently found in a Taiwanese PD family were tested for association with the disease in a sample of 608 PD cases and 373 ethnically matched controls. Heterozygosity for the Gly2385Arg variant was significantly more frequent among PD patients than controls (nominal p value=0.004, corrected for multiple comparisons=0.012, gender- and age-adjusted odds ratio=2.24, 95% C.I.: 1.29-3.88); this variant was uniformly distributed across genders and age strata. Two novel variants, Met1869Val and Glu1874Stop, were found in one PD case each; their pathogenic role remains, therefore, uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were present with similar frequency in cases and controls, and were therefore, interpreted as disease-unrelated polymorphisms. Our findings suggest that the LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which acts as common risk factor for sporadic PD in the population of Chinese ethnicity.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
Issue number3
Publication statusPublished - Jul 2006


  • LRRK2
  • Mutation
  • Parkinson's disease
  • Polymorphism
  • Risk factor
  • Taiwan

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuroscience(all)


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