LRRK2 Gly2385Arg variant is a risk factor of Parkinson’s disease among Han‐Chinese from mainland China

Abstract

Mutations in the gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been recently linked with autosomal-dominant parkinsonism, and polymorphisms have been commonly associated with sporadic Parkinson's disease (PD). A p.2385G>R variant has been reported as a risk factor for PD in Taiwan, Singapore and Japan. Herein, we have assessed the frequency of this polymorphism among the ethnic Han-Chinese population in a case-control study. A total of 600 patients with PD and 334 unrelated healthy controls were genotyped using PCR-restriction fragment length polymorphism analysis. Hardy-Weinberg equilibrium of each group was calculated, and differences in genotype frequencies between groups were assessed by the Chi-square test. In the PD cohort, 70 patients (11.7%) were heterozygous and 1 (0.2%) was homozygous for the p.2385G>R variant. This was significantly more frequent than in the controls [3.3%, Odds ratio = 3.9, 95% confidence interval (CI) = 2.1-7.5, P < 0.01]. Clinically, the age of PD onset of the p.2385G>R carriers was lower than the non-carriers (P = 0.01). Our study indicates that this LRRK2 p.2385G>R substitution contributes to the development of PD in ethnic Han-Chinese population, which may play important implications for future study on molecular genetics and pathogenesis of PD.

Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease

“…1 FTLD is the second most common cause of presenile dementia after Alzheimer's disease (AD) [1][2][3] and accounts for 5 to 10% of neurodegenerative dementias in epidemiological samples and between 9 and 16% in autopsy series. 1 Clinical subtypes of FTLD include (1) a behavioral variant with predominant frontotemporal involvement, (2) semantic dementia, and (3) primary progressive aphasia.…”

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson’s disease in the Chinese population

“…This work led to our initial identification of the association of Gly2385Arg with PD, a finding that has been rapidly and consistently replicated in Chinese populations from Singapore [5], Taiwan [6,7], mainland China [8,9], and in the Japanese population [10].…”

Comprehensive mutational analysis of LRRK2 reveals variants supporting association with autosomal dominant Parkinson's disease

“…16,17,[34][35][36][37][38][39] One of these studies included 26 patients with a familial history of PD, among which six patients were p.G2385R carriers. 40 A meta-analysis on the basis of these studies involving 2205 PD patients and 1817 controls demonstrated average carrier rates of 9.3% in PD and 4% in controls.…”