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

被引:0
作者
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
机构
[1] Erasmus MC Rotterdam,Department of Clinical Genetics
[2] Chang Gung Memorial Hospital,Neuroscience Research Center
[3] Chang Gung University College of Medicine,Department of Neurology
[4] Chang Gung Memorial Hospital,Human Molecular Genetics Laboratory
[5] Chang Gung University College of Medicine,Centro Dino Ferrari, Department of Neurological Sciences
[6] Chang Gung Memorial Hospital,National Centre of Epidemiology
[7] Chang Gung University College of Medicine,undefined
[8] University of Milan,undefined
[9] and Foundation “Ospedale Maggiore Policlinico,undefined
[10] National Institute for Health,undefined
来源
Neurogenetics | 2006年 / 7卷
关键词
Parkinson’s disease; Mutation; Polymorphism; Risk factor; Taiwan;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:133 / 138
页数:5
相关论文
共 50 条
[31]   LRRK2 G2385R variant carriers of female Parkinson’s disease are more susceptible to motor fluctuation [J].
Chao Gao ;
Hao Pang ;
Xiao-Guang Luo ;
Yan Ren ;
Hong Shang ;
Zhi-Yi He .
Journal of Neurology, 2013, 260 :2884-2889
[32]   The association between the LRRK2 G2385R variant and the risk of Parkinson’s disease: a meta-analysis based on 23 case–control studies [J].
Cheng-long Xie ;
Jia-Lin Pan ;
Wen-Wen Wang ;
Yu Zhang ;
Su-fang Zhang ;
Jing Gan ;
Zhen-Guo Liu .
Neurological Sciences, 2014, 35 :1495-1504
[33]   A Comprehensive Analysis of Population Differences in LRRK2 Variant Distribution in Parkinson's Disease [J].
Shu, Li ;
Zhang, Yuan ;
Sun, Qiying ;
Pan, Hongxu ;
Tang, Beisha .
FRONTIERS IN AGING NEUROSCIENCE, 2019, 11
[34]   LRRK2 P755L variant in sporadic Parkinson’s disease [J].
Hiroyuki Tomiyama ;
Ikuko Mizuta ;
Yuanzhe Li ;
Manabu Funayama ;
Hiroyo Yoshino ;
Lin Li ;
Miho Murata ;
Mitsutoshi Yamamoto ;
Shin-ichiro Kubo ;
Yoshikuni Mizuno ;
Tatsushi Toda ;
Nobutaka Hattori .
Journal of Human Genetics, 2008, 53 :1012-1015
[35]   LRRK2 Pro755Leu variant in ethnic Chinese population with Parkinson's disease [J].
Yao, Ling-yan ;
Guo, Ji-feng ;
Wang, Lei ;
Yu, Ren-he ;
Sun, Qi-ying ;
Pan, Qian ;
Xia, Kun ;
Tang, Bei-sha ;
Shen, Lu .
NEUROSCIENCE LETTERS, 2011, 495 (01) :35-38
[36]   LRRK2 P755L variant in sporadic Parkinson's disease [J].
Tomiyama, Hiroyuki ;
Mizuta, Ikuko ;
Li, Yuanzhe ;
Funayama, Manabu ;
Yoshino, Hiroyo ;
Li, Lin ;
Murata, Miho ;
Yamamoto, Mitsutoshi ;
Kubo, Shin-ichiro ;
Mizuno, Yoshikuni ;
Toda, Tatsushi ;
Hattori, Nobutaka .
JOURNAL OF HUMAN GENETICS, 2008, 53 (11-12) :1012-1015
[37]   Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population [J].
Chen, Si ;
Liu, Hong ;
Wu, Qian-qian ;
Xu, Shu-jun ;
Li, Wei-guo ;
Chen, Teng ;
Li, Chao ;
Ma, Xiang-yu ;
Xu, Shuo ;
Liu, Yi-ming .
FRONTIERS IN NEUROLOGY, 2019, 10
[38]   Molecular biology changes associated with LRRK2 mutations in Parkinson's disease [J].
Lu, Yi Wei ;
Tan, Eng-King .
JOURNAL OF NEUROSCIENCE RESEARCH, 2008, 86 (09) :1895-1901
[39]   The Cell Biology of LRRK2 in Parkinson's Disease [J].
Usmani, Ahsan ;
Shavarebi, Farbod ;
Hiniker, Annie .
MOLECULAR AND CELLULAR BIOLOGY, 2021, 41 (05)
[40]   Lrrk2 pathogenic substitutions in Parkinson's disease [J].
Mata, IF ;
Kachergus, JM ;
Taylor, JP ;
Lincoln, S ;
Aasly, J ;
Lynch, T ;
Hulihan, MM ;
Cobb, SA ;
Wu, RM ;
Lu, CS ;
Lahoz, C ;
Wszolek, ZK ;
Farrer, MJ .
NEUROGENETICS, 2005, 6 (04) :171-177