The association between the LRRK2 G2385R variant and the risk of Parkinson's disease: a meta-analysis based on 23 case-control studies

Clinical diagnosis of Parkinson's disease (PD) is essential but misdiagnosis of PD-like diseases is quite common. LRRK2 G2385R variants have been extensively examined for the association to the risk of Parkinson's disease. However, results from different studies are inconsistent. The purpose of this meta-analysis was to assess the association between the LRRK2 G2385R variants and the risk of PD. A systematic literature search was performed for 6 databases up to January of 2014 to identify case-control studies involving LRRK2 G2385R variants and the risk of PD. A total of 12,915 cases and 12,451 controls in 23 case-control studies were included in this meta-analysis. The results indicated that the variant A allele carriers (GA + AA) increased risk of PD when compared with the homozygote GG (GA + AA vs. GG: OR = 2.4, 95 % CI = 1.97 to 2.92, P < 0.00001). In the subgroup analysis by ethnicity, increased risks were identified among Chinese (OR = 2.69, 95 % CI = 2.1-3.45, P < 0.00001) as well as in non-Chinese (OR = 2.17, 95 % CI 1.75-2.69, P < 0.00001). In the subgroup analysis by age of onset, significant associations were found in both later-onset PD (LOPD) and early-onset PD (EOPD) cases. And there was no significant difference of the allele frequency between patients with LOPD and EOPD (OR = 1.18, 95 % CI = 0.77-1.80, P = 0.45). Our results suggest that the LRRK2 G2385R variants contribute to the susceptibility of PD especially in Chinese PD. Meanwhile, it is possible that age is not the risk factor to facilitate G2385R gene mutation.