title: LRRK2 Gly2385Arg variant is a risk factor of Parkinson's disease among Han-Chinese from mainland China.
abstract: Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385G>R variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385G>R variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P < 0.01]. Clinically, the age of PD onset of the p.2385G>R carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385G>R substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.
authors.affiliation: Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: X-K
authors.initials: XK
authors.lastname: An
authors.forename: R
authors.initials: R
authors.lastname: Peng
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: J-M
authors.initials: JM
authors.lastname: Burgunder
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: W-J
authors.initials: WJ
authors.lastname: Chen
authors.forename: J-H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wang
authors.forename: Y-M
authors.initials: YM
authors.lastname: Xu
authors.forename: Y-R
authors.initials: YR
authors.lastname: Gou
authors.forename: G-G
authors.initials: GG
authors.lastname: Yuan
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics*; D044466:Asian People / Q000208:ethnology; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
chemical_list: D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine