The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population.
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%.
Lu
Chin-Song
CS
Neuroscience Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan. c81214@adm.cgmh.org.tw
Wu-Chou
Yah-Huei
YH
van Doeselaar
Marina
M
Simons
Erik J
EJ
Chang
Hsiu-Chen
HC
Breedveld
Guido J
GJ
Di Fonzo
Alessio
A
Chen
Rou-Shayn
RS
Weng
Yi-Hsin
YH
Lai
Szu-Chia
SC
Oostra
Ben A
BA
Bonifati
Vincenzo
V
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
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases