LRRK2 Gly2385Arg variant is a risk factor of Parkinson's disease among Han-Chinese from mainland China.
Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385G>R variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385G>R variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P < 0.01]. Clinically, the age of PD onset of the p.2385G>R carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385G>R substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.
An
X-K
XK
Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Peng
R
R
Li
T
T
Burgunder
J-M
JM
Wu
Y
Y
Chen
W-J
WJ
Zhang
J-H
JH
Wang
Y-C
YC
Xu
Y-M
YM
Gou
Y-R
YR
Yuan
G-G
GG
Zhang
Z-J
ZJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics*; D044466:Asian People / Q000208:ethnology; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors
D001120:Arginine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine