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.

Keywords: GAK; GWAS; HLA; Parkinson's disease; Taiwanese.