Association of Common Variants in the Glucocerebrosidase Gene with High Susceptibility to Parkinson's Disease among Chinese.

The genetic variants in glucocerebrosidase (GBA) gene have been previously examined as potential susceptibility factors for Parkinson's disease (PD). Although of great interest, possible role of GBA gene in PD has not been well investigated in eastern Chinese population. To explore this association, we conducted a genetic screen of three common GBA variants (p.L444P, p.N370S, and p.R120W) in a casecontrol cohort comprised of 638 subjects of Chinese ethnicity. In order to provide a more precise estimate of this association, a meta-analysis was performed. We found that the GBA p.L444P allele was significantly more frequent (P = 0.001) in the PD patients (6/195 = 3.08%) than in the controls (0/443). The p.L444P mutation, but not p.N370S and p.R120W, was found to be associated with PD. Combined analysis including all previously published ancestral Chinese data yielded a highly significant association between the GBA gene and an increased risk for PD (OR = 8.13, 95% CI, 4.43-14.92, P < 0.00001). Our study suggests that the GBA gene may be a susceptibility gene for PD in the Chinese population. Efforts to elucidate in detail this interesting and biologically plausible genetic association are warranted.

Association analysis of PARK16-18 variants and Parkinson's disease in a Chinese population.

Genome-wide association studies identified PARK16 variants rs823128 and rs947211, PARK17/GAK rs11248051 and PARK18/HLA-DRA rs3129882 as risk factors for Parkinson's disease (PD). However the susceptibility of these loci to predisposing individuals for PD, particularly rs11248051, remains under investigation in Chinese populations. A total of 323 PD patients and 345 age and sex matched controls were recruited in eastern China. Our results show that minor allele frequencies of rs11248051 (odds ratio [OR] 1.522; p=0.016) and rs3129882 (OR 1.294; p=0.03), but not rs823128 and rs947211, were associated with risk for PD. Genetic interaction analysis revealed that subjects simultaneously carrying the T allele (TC or TT) of rs11248051 and the A allele (AG or AA) of rs3129882 had an aggravated risk (OR 1.91; p=0.016) of PD. However, rs11248051 or rs3129882 displayed no association with PD phenotypes or clinical scores. Our results suggest that rs11248051 and rs3129882 are risk factors for sporadic PD in a Chinese population, and their genetic interplay contributes to an elevated risk for PD predisposition. Our data provide a novel insight and further information regarding PARK16-18 loci in PD susceptibility.