LRRK2 G2385R variant carriers of female Parkinson’s disease are more susceptible to motor fluctuation

Gao, Chao; Pang, Hao; Luo, Xiaoguang; Ren, Yan; Shang, Hong; He, Zhiwei

doi:10.1007/s00415-013-7086-9

Cited by 19 publications

(22 citation statements)

References 26 publications

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“…These participants also more commonly had motor fluctuations. The finding of a higher frequency of motor fluctuations is consistent with prior work from other Chinese investigators . Recently a comparison between iPD and 3 LRRK2 risk variants seen in Asian populations (G2385R, R1628P, or S1647T) found that UPDRS motor scores worsened more rapidly in LRRK2 variant carriers after a disease duration of 4 years .…”

Section: Discussionsupporting

confidence: 89%

“…It is interesting that dyskinesias (in contrast to motor fluctuations) were not more common in LRRK2 G2385R PD. Prior work is conflicting on this topic, with 1 report suggesting increased frequency dyskinesias (albeit to a lesser extent than motor fluctuations) 27 and another not finding any increase in dyskinesias. The apparent discordance between dyskinesias and motor fluctuations could be specific to G2385R mutations or may reflect other aspects of genetic susceptibility in Chinese populations.…”

Section: Discussionmentioning

confidence: 99%

“…The finding of a higher frequency of motor fluctuations is consistent with prior work from other Chinese investigators. 27 Recently a comparison between iPD and 3 LRRK2 risk variants seen in Asian populations (G2385R, R1628P, or S1647T) found that UPDRS motor scores worsened more rapidly in LRRK2 variant carriers after a disease duration of 4 years. 28 Although ON-condition scores are not a direct reflection of the state of neurodegeneration, these findings suggest that PD related to the G2385R mutation may be more rapidly progressive, which contrasts with the general perception that LRRK2-associated PD has a more benign phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Motor and nonmotor heterogeneity of LRRK2‐related and idiopathic Parkinson's disease

et al. 2016

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Motor and nonmotor heterogeneity of LRRK2‐related and idiopathic Parkinson's disease

et al. 2016

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“…Genetic variants, such as DRD3 G3127A in the dopamine receptor (DR) gene have been shown to be involved in L-dopa-induced dyskinesia (Comi et al, 2017 ). G2385R in LRRK2 was previously found to be significantly associated with motor complications in female PD patients (Gao et al, 2013 ). Our analysis demonstrated that G2019S or G2385R carriers tend to develop motor complications with significant differences, consistent with higher LEDD, relative to non-carriers (Cacabelos, 2017 ).…”

Section: Discussionmentioning

confidence: 90%

Clinical Heterogeneity Among LRRK2 Variants in Parkinson's Disease: A Meta-Analysis

Zhang

Pan

et al. 2018

Front. Aging Neurosci.

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Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Variants in the LRRK2 gene have been shown to be associated with PD. However, the clinical characteristics of LRRK2-related PD are heterogeneous. In our study, we performed a comprehensive pooled analysis of the association between specific LRRK2 variants and clinical features of PD.Methods: Articles from the Medline, Embase, and Cochrane databases were included in the meta-analysis. Strict inclusion criteria were applied, and detailed information was extracted from the final original articles included. Revman 5.3 software was used for publication biases and pooled and sensitivity analyses.Results: In all, 66 studies having the clinical manifestations of PD patients with G2019S, G2385R, R1628P, and R1441G were included for the final analysis. The prominent clinical features of LRRK2-G2019S-related PD patients were female sex, higher rates of early-onset PD (EOPD), and family history (OR: 0.77 [male], 1.37, 2.62; p < 0.00001, 0.02, < 0.00001). PD patients with G2019S were more likely to have high scores of Schwab & England (MD: 1.49; p < 0.00001), low GDS scores, high UPSIT scores (MD: 0.43, 4.70; p = 0.01, < 0.00001), and good response to L-dopa (OR: 2.33; p < 0.0001). Further, G2019S carriers had higher LEDD (MD: 115.20; p < 0.00001) and were more likely to develop motor complications, such as dyskinesia and motor fluctuations (OR: 2.18, 2.02; p < 0.00001, 0.04) than non-carriers. G2385R carriers were more likely to have family history (OR: 2.10; p = 0.007) than non-G2385R carriers and lower H-Y and higher MMSE scores (MD: −0.13, 1.02; p = 0.02, 0.0007). G2385R carriers had higher LEDD and tended to develop motor complications, such as motor fluctuations (MD: 53.22, OR: 3.17; p = 0.01, < 0.00001) than non-carriers. Other clinical presentations did not feature G2019S or G2385R. We observed no distinct clinical features for R1628P or R1441G. Our subgroup analyses in different ethnic group for specific variant also presented with relevant clinical characteristics of PD patients.Conclusions: Clinical heterogeneity was observed among LRRK2-associated PD in different variants in total and in different ethnic groups, especially for G2019S and G2385R.

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“…Therefore, 23 papers were selected for further full text review. Four papers were not case-control studies [21–24]; one was a review [25]; four did not provide detailed genotype data [26–29]. Finally, we identified fourteen eligible papers [7–20] including nineteen studies in this meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

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

Zhao

Kong

2016

Oncotarget

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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.

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LRRK2 G2385R variant carriers of female Parkinson’s disease are more susceptible to motor fluctuation

Cited by 19 publications

References 26 publications

Motor and nonmotor heterogeneity of LRRK2‐related and idiopathic Parkinson's disease

Motor and nonmotor heterogeneity of LRRK2‐related and idiopathic Parkinson's disease

Clinical Heterogeneity Among LRRK2 Variants in Parkinson's Disease: A Meta-Analysis

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

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