Penetrance of LRRK2 G2385R and R1628P is modified by common PD-associated genetic variants

Wang, Chaodong; Cai, Yanning; Zhang, Zheng; Tang, Beisha; Xu, Yanming; Wang, Tao; Ma, Jinghong; Chen, Shengdi; Langston, J. William; Tanner, Caroline M.; Chan, Piu

doi:10.1016/j.parkreldis.2012.05.003

Cited by 61 publications

(54 citation statements)

References 37 publications

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“…Totally, 14 studies711131520212223242526272829 were included from across all the ethnic Han-Chinese population that mainly located in Mainland China, Singapore and Taiwan. Process of searching for and screening studies was showed in Figure S1.…”

Section: Resultsmentioning

confidence: 99%

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Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population

Zhang

Wang

Jiao

et al. 2016

Sci Rep

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Recent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson’s disease (PD). The R1628P variant of LRRK2 may be a specific risk factor for PD in ethnic Han-Chinese populations. This study is to elucidate the epidemiological feature of R1628P in ethnic Han-Chinese population with PD. A comprehensive meta-analysis was performed to evaluate the precise association between R1628P variant and the risk for PD in ethnic Han-Chinese and subgroups stratified by gender, onset age, or family history. The analysis assessing the role of R1628P on the risk of PD in ethnic Han-Chinese supported a significant association, and the odds ratio was 1.86. We further estimate the specific prevalence in relevant ethnic Han-Chinese subgroups. After stratifying the eligible data by gender, onset age, or family history, significant associations were found in all male, female, early-onset, late-onset, familial and sporadic subgroups, and the odds ratio were 1.90, 1.94, 2.12, 1.75, 6.71 and 1.81 respectively. In conclusion, our meta-analysis suggests that R1628P variant of LRRK2 has a significant association with the risk of PD in ethnic Han-Chinese and subgroup population.

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Section: Resultsmentioning

confidence: 99%

“…Only 2 studies722 in ethnic Han-Chinese with familial PD and 11 studies711152021232425262728 in ethnic Han-Chinese with sporadic PD were analyzed to evaluate the overall level for association between familial (Fig. 4A) or sporadic (Fig.…”

Section: Resultsmentioning

confidence: 99%

Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population

Zhang

Wang

Jiao

et al. 2016

Sci Rep

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“…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. Selection for eligible papers included in this meta-analysis was presented in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent studies have further investigated the association between the R1628P polymorphism and the risk of PD but produced conflicting results [8–20]. However, these discrepancies may be due inadequate statistical power, different ethnic populations, and small sample sizes.…”

Section: Introductionmentioning

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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“…A standard clinical neurological examination was performed for all the patients by 2 neurologists, and a diagnosis of idiopathic PD was made according to the United Kingdom PD Brain Bank Criteria (Hughes et al, 1992). To eliminate other genetic factors effects, we did not include the patients or controls with GBA (L444P, F213I, R353W, and N370S) (Sun et al, 2010), LRRK2 (G2385R and R1628P) (Wang et al, 2012), and SMPD1 (L302P) mutations. Patients with abnormal rearrangements in Parkin, SNCA, PINK1, ATP13A2, LRRK2, and DJ-1 were also excluded (tested by SALSA MLPA kits P051, MRC Holland, Amsterdam, The Netherlands).…”

Section: Study Populationmentioning

confidence: 99%

LRRK2 A419V variant is a risk factor for Parkinson's disease in Asian population

Tang

Liu

et al. 2015

Neurobiology of Aging

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Penetrance of LRRK2 G2385R and R1628P is modified by common PD-associated genetic variants

Cited by 61 publications

References 37 publications

Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population

Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population

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

LRRK2 A419V variant is a risk factor for Parkinson's disease in Asian population

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