title: The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population.
abstract: 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] approximately 4%) and Gly2385Arg variants (PAR approximately 6%) yields a total PAR of approximately 10%.
authors: Neuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. c81214@adm.cgmh.org.tw
authors: Chin-Song
authors: CS
authors: Lu
authors: Yah-Huei
authors: YH
authors: Wu-Chou
authors: Marina
authors: M
authors: van Doeselaar
authors: Erik J
authors: EJ
authors: Simons
authors: Hsiu-Chen
authors: HC
authors: Chang
authors: Guido J
authors: GJ
authors: Breedveld
authors: Alessio
authors: A
authors: Di Fonzo
authors: Rou-Shayn
authors: RS
authors: Chen
authors: Yi-Hsin
authors: YH
authors: Weng
authors: Szu-Chia
authors: SC
authors: Lai
authors: Ben A
authors: BA
authors: Oostra
authors: Vincenzo
authors: V
authors: Bonifati
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D017386:Sequence Homology, Amino Acid; D013624:Taiwan
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases