title: The LRRK2 R1628P variant plays a protective role in Han Chinese population with Alzheimer's disease.
abstract: OBJECTIVE
  Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine-rich repeat kinase 2 (LRRK2) have been reported to be responsible for PD, and the location of LRRK2 is within a linkage peak for sporadic AD (SAD). The aim of this study was to investigate two Asian-specific LRRK2 variants, R1628P and G2385R, with the association of Han Chinese SAD.
  
  
  METHODS
  Genotyping of R1628P and G2385R was performed by PCR-restriction fragment length polymorphism (RFLP) analysis in 390 patients with SAD and 545 unrelated age- and sex-matched healthy controls.
  
  
  RESULTS
  The frequency of the C allele within R1628P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) (OR 0.264; 95% CI, 0.088-0.792, P = 0.018). After stratification by the presence of one or two apolipoprotein E ε4 alleles, the protective effect becomes stronger (ε44: OR 0.028; 95% CI, 0.003-0.303, P = 0.003; ε4: OR 0.104; 95% CI, 0.013-0.818, P = 0.031). However, no difference was found in G2385R variant.
  
  
  CONCLUSIONS
  Our study suggested that R1628P variant within LRRK2 plays a protective role in Han Chinese population with SAD and such effect has an interaction with the APOE genotype.
authors: Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Hong-Lei
authors: HL
authors: Li
authors: Shen-Ji
authors: SJ
authors: Lu
authors: Yi-Min
authors: YM
authors: Sun
authors: Qi-Hao
authors: QH
authors: Guo
authors: Adele Dessa
authors: AD
authors: Sadovnick
authors: Zhi-Ying
authors: ZY
authors: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics* / Q000517:prevention & control*; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases