title: Reaffirmation of GAK, but not HLA-DRA, as a Parkinson's disease susceptibility gene in a Taiwanese population.
abstract: Recent genome-wide association studies of Parkinson's disease (PD) in Caucasian populations have identified two new susceptibility loci, GAK and HLA-DRA; however, only limited information exists regarding the involvement of these genes in PD risk in other ethnic groups. Here, we examined whether these genetic effects were consistent in a Taiwanese PD population. In a total 900 participants, including 448 PD patients and 452 control subjects, we genotyped the rs11248051 and rs1564282 variants of GAK, and the rs3129882 variant of HLA-DRA. Logistic regression analysis was used to test for associations between genotype and PD under an additive model, adjusting for age and gender. Subjects with CT/TT genotypes of GAK rs11248051 had a modestly increased association with PD compared to those with CC genotype (OR = 1.37; 95% CI = 1.09, 1.87; P = 0.03). Carriers and non-carriers exhibited indistinguishable phenotypes in regards to clinical presentation and onset age. We observed no association between PD risk and GAK rs1564282 or HLA-DRA rs3129882 variant. The different genetic effects between Taiwanese and Caucasian populations may come from differences in population structure and geographic region-specific genetic-environmental interactions. In conclusion, our results supported the association between the rs11248051 variant in GAK and PD risk in a Taiwanese population. Future functional studies of GAK in neuronal degeneration are warranted to unravel its role in the pathogenetic mechanism of PD.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.forename: Meng-Ling
authors.initials: ML
authors.lastname: Chen
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Tai
authors.forename: Chin-Yi
authors.initials: CY
authors.lastname: Yu
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D059805:HLA-DR alpha-Chains / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D013624:Taiwan; D055815:Young Adult
chemical_list: D059805:HLA-DR alpha-Chains; D047908:Intracellular Signaling Peptides and Proteins; C486325:GAK protein, human; D017346:Protein Serine-Threonine Kinases
keywords: GAK; GWAS; HLA; Parkinson's disease; Taiwanese