title: A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Erasmus MC Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Yah-Huei
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: Chin-Song
authors.initials: CS
authors.lastname: Lu
authors.forename: Marina
authors.initials: M
authors.lastname: van Doeselaar
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Simons
authors.forename: Christan F
authors.initials: CF
authors.lastname: Rohé
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Chang
authors.forename: Rou-Shayn
authors.initials: RS
authors.lastname: Chen
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Weng
authors.forename: Nicola
authors.initials: N
authors.lastname: Vanacore
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Breedveld
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bonifati
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013624:Taiwan
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases