title: MAPT IVS1+124 C>G modifies risk of LRRK2 G2385R for Parkinson's disease in Chinese individuals.
abstract: Variants of the MAPT gene have been suggested to be associated with Parkinson's disease (PD) and to modify the risk for leucine-rich repeat kinase 2 (LRRK2) Parkinsonism. However, this has not been confirmed in Asians with ethnicity-specific variants of MAPT and LRRK2. In this study, Asian-specific LRRK2 p.G2385R variant and IVS1+124 C>G, a functional single-nucleotide polymorphism located in the MAPT promoter region, were genotyped in 561 Chinese PD patients and 556 control subjects. Allelic and genotypic frequencies of the 2 variants were compared between cases and control subjects independently and in combination. As a result, the LRRK2 p.G2385R variant alone was associated with an increased risk for PD (Odds ratio, 1.86; 95% confidence intervals, 1.08-3.19; p = 0.014), whereas MAPT IVS1+124 C>G was not (p = 0.34). However, the coexistence of MAPT IVS1+124C>G significantly enhanced the LRRK2 G2385R-conferred risk for PD (Odds ratio, 2.30; 95% confidence intervals, 1.14-4.54; p = 0.012). These results provide further evidence supporting the interaction between MAPT and LRRK2 genes, which increases the susceptibility to PD in Chinese individuals.
authors.affiliation: Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing, China; Key Laboratory on Parkinson's Disease of Beijing, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Dan
authors.affiliation: Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing, China; Key Laboratory on Parkinson's Disease of Beijing, Beijing, China; Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Chinese National Human Genome Center, Beijing, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Feng
authors.affiliation: Chinese National Human Genome Center, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing, China; Key Laboratory on Parkinson's Disease of Beijing, Beijing, China; Parkinson's Disease Center of Beijing Institute of Brain Disorders, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing, China; Key Laboratory on Parkinson's Disease of Beijing, Beijing, China; Chinese National Human Genome Center, Beijing, China; Parkinson's Disease Center of Beijing Institute of Brain Disorders, Beijing, China. Electronic address: pbchan90@gmail.com.
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012306:Risk; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: Genetic association; Interaction; LRRK2; MAPT; Parkinson's disease