Relationship between LRRK2 R1628P polymorphism and Parkinson's disease in Asian populations

Abstract

Although the leucine-rich repeat kinase 2 (LRRK2) R1628P polymorphism has been associated with the risk of Parkinson's disease (PD) in Taiwan, China, and Singapore, there are conflicting findings regarding this relationship. Thus, the aim of the present meta-analysis was to evaluate the associations between the LRRK2 R1628P polymorphism (rs33949390) and PD in Asian populations. A search for eligible studies was performed in PubMed, Embase, SinoMed, and the China Knowledge Resource Integrated Database, and pooled odds ratios and 95% confidence intervals were used to evaluate the strength of the association between the R1628P polymorphism and PD. This meta-analysis assessed 19 studies from 14 papers that involved a total of 9,927 PD patients and 8,602 controls and found that the R1628P polymorphism was significantly associated with the risk of PD in Asian populations. Moreover, stratification analyses indicated that the R1628P polymorphism was significantly associated with an increased risk of PD among Chinese as well as non-Chinese Asian populations and an increased risk of PD in Chinese patients from China, Taiwan, and Singapore. In a stratified analysis conducted according to age, significant associations were found for both late-onset PD and early-onset PD. The present data indicate that the R1628P polymorphism of the LRRK2 gene contributes to PD susceptibility in Asian, especially Chinese, populations.

A Comprehensive Analysis of Population Differences in LRRK2 Variant Distribution in Parkinson's Disease

“…Previous studies of ethnicity-specific LRRK2 variation have focused primarily on the common variants G2019S, G2385R, and R1628P (Xie et al, 2014; Liu et al, 2016; Zhang et al, 2016; Zhao and Kong, 2016), showing that G2019S was more common in European and North American populations while G2385R and R1628P existed only in Asian populations (Guo et al, 2006). Our study replicated these results, and further demonstrated the importance of other variants, such as P755L, A419V, and R1398H.…”

“…To date, nearly a hundred LRRK2 variants have been identified. Of these, G2019S, R1628P, and G2385R have traditionally received much of the attention, and there have already been a number of meta-analyses on the role of these variants in PD risk in people of different ethnicities (Xie et al, 2014; Liu et al, 2016; Zhang et al, 2016; Zhao and Kong, 2016). These variants each possess distinct geographical distributions.…”

LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson’s Disease Cohort from Kazakhstan

“…4.3. p.Arg1628Pro. Regarding p.Arg1628Pro, data from a meta-analysis, including 19 studies with a total of 9,927 PD patients and 8,602 controls, suggest that the variant is significantly associated with the risk of PD in East Asian populations [34]. We failed to find this variant in our PD patients but it was present in controls.…”

The Development and Design Strategy of Leucine-Rich Repeat Kinase 2 Inhibitors: Promising Therapeutic Agents for Parkinson’s Disease

“…It is particularly high among Ashkenazi Jews (29%) and North African Berbers (37%) . Additionally, the G2385R mutation in the WD40 domain and the R1628P mutation in the COR domain are reported to contribute to PD susceptibility in the Chinese population. , As the complicated LRRK2 activation mechanism is regulated at multiple levels, any amino acid substitution affecting the enzyme core or any PPI interface impede its function. According to experimental findings, different mutations lead to distinct abnormalities in the activation mechanism.…”