title: Genetic variants ofLRRK2 in Taiwanese Parkinson's disease.
abstract: Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset ≤ 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.
authors: Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
authors: Yih-Ru
authors: YR
authors: Wu
authors: Kuo-Hsuan
authors: KH
authors: Chang
authors: Wen-Teng
authors: WT
authors: Chang
authors: Ya-Chin
authors: YC
authors: Hsiao
authors: Hsuan-Chu
authors: HC
authors: Hsu
authors: Pei-Ru
authors: PR
authors: Jiang
authors: Yi-Chun
authors: YC
authors: Chen
authors: Chih-Ying
authors: CY
authors: Chao
authors: Yi-Chung
authors: YC
authors: Chang
authors: Bo-Hsun
authors: BH
authors: Lee
authors: Fen-Ju
authors: FJ
authors: Hu
authors: Wan-Ling
authors: WL
authors: Chen
authors: Guey-Jen
authors: GJ
authors: Lee-Chen
authors: Chiung-Mei
authors: CM
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases