The LRRK2 Arg1628Pro variant is a risk factor for Parkinson’s disease in the Chinese population

被引：0
作者：
Chin-Song Lu
Yah-Huei Wu-Chou
Marina van Doeselaar
Erik J. Simons
Hsiu-Chen Chang
Guido J. Breedveld
Alessio Di Fonzo
Rou-Shayn Chen
Yi-Hsin Weng
Szu-Chia Lai
Ben A. Oostra
Vincenzo Bonifati
机构：
[1] Chang Gung Memorial Hospital,Neuroscience Research Center
[2] Chang Gung University,Department of Neurology
[3] Chang Gung Memorial Hospital,Human Molecular Genetics Laboratory
[4] Chang Gung Memorial Hospital,Department of Neurology
[5] Department of Clinical Genetics,undefined
[6] Chang Gung Memorial Hospital,undefined
来源：
Neurogenetics | 2008年 / 9卷
关键词：
Parkinson’s disease; Genetics; LRRK2; Association; Risk allele;
D O I：
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学科分类号：
摘要：
The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson’s disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29–3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson’s disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson’s disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ~4%) and Gly2385Arg variants (PAR ~6%) yields a total PAR of ~10%.
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[1]  
Zimprich A(2004)Mutations in LRRK2 cause autosomal-dominant Parkinsonism with pleomorphic pathology Neuron 44 601-607
[2]  
Biskup S(2004)Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease Neuron 44 595-600
[3]  
Leitner P(2007)LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking familial and sporadic Parkinson’s disease Neurochem Res 32 1700-1708
[4]  
Lichtner P(2006)A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson’s disease risk in Taiwan Neurogenetics 7 133-138
[5]  
Farrer M(2007)The LRRK2 Gly2385Arg variant is associated with Parkinson’s disease: genetic and functional evidence Hum Genet 120 857-863
[6]  
Lincoln S(2006)A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan BMC Neurol 6 47-92
[7]  
Paisan-Ruiz C(2007)Lrrk2 G2385R is an ancestral risk factor for Parkinson’s disease in Asia Parkinsonism Relat Disord 13 89-2443
[8]  
Jain S(2007)The prevalence of LRRK2 Gly2385Arg variant in Chinese Han population with Parkinson’s disease Mov Disord 22 2439-305
[9]  
Evans EW(2008)LRRK2 Gly2385Arg variant is a risk factor of Parkinson’s disease among Han-Chinese from mainland China Eur J Neurol 15 301-275
[10]  
Gilks WP(2007)Leucine-rich repeat kinase 2 G2385R variant is a risk factor for Parkinson disease in Asian population Neuroreport 18 273-184
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