title: Association of GCH1 and MIR4697, but not SIPA1L2 and VPS13C polymorphisms, with Parkinson's disease in Taiwan.
abstract: Recently, a large-scale meta-analysis of genome-wide association study (GWAS) data identified several new risk loci that can modulate the risk of Parkinson's disease (PD). These associations have yet to be examined in PD patients in Chinese or Asian population. Because ethnic-specific effect is an important concern for GWAS analysis, we genotyped single-nucleotide polymorphisms in the new genetic loci, GCH1 (rs11158026), SIPA1L2 (rs10797576), VPS13C (rs2414739), and MIR4697 (rs329648), to investigate their associations with risk of PD in Taiwan. Another single-nucleotide polymorphism GCH1 rs7155501, previously identified by GWAS listed at the top 20 genes in PDGene database was also included. A total of 1151 study subjects comprising 598 patients with PD and 553 unrelated healthy controls were recruited. The frequency of minor allele (C allele) of GCH1 rs11158026 was found to be significantly higher in PD cases than in controls (p = 0.003). The CC genotype of rs11158026 increased PD risk compared to TT genotype (odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.09, 1.53, p = 0.004). Under additive model, the GCH1 rs11158026 increased the risk of developing PD (OR = 1.30, 95% CI = 1.10, 1.54, p = 0.002). In recessive model, the genotype TT of MIR4697 rs329648 marginally decreased the PD risk (OR = 0.62, 95% CI = 0.43, 0.90, p = 0.01). The PD patients demonstrated similar genotypic and allelic frequencies in GCH1 rs7155501, SIPA1L2 rs10797576, and VPS13C rs2414739 with the controls. These findings suggest that the GCH1 and MIR4697 but not SIPA1L2 and VPS13C are genetic loci influencing risk of PD in Taiwan.
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chiung-Mei
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Medicine and Surgery MBChB, School of Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Mu-Chun
authors.initials: MC
authors.lastname: Chiang
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Hon-Chung
authors.initials: HC
authors.lastname: Fung
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Chang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Guey-Jen
authors.initials: GJ
authors.lastname: Lee-Chen
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: yihruwu@cloud.cgmh.org.tw.
authors.forename: Yih-Ru
authors.initials: YR
authors.lastname: Wu
mesh_terms: D016022:Case-Control Studies; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D020690:GTPase-Activating Proteins / Q000235:genetics; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012306:Risk; D013624:Taiwan; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D011506:Proteins; C490403:SIPA1 protein, human; C495324:VPS13C protein, human; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases; D006136:GTP Cyclohydrolase
keywords: Disease association; GCH1; MIR4697; Parkinson's disease; SIPA1L2; Single-nucleotide polymorphism; VPS13C