Quantitative assessment of the effect of LRRK2 exonic variants on the risk of Parkinson’s disease: A meta-analysis

Wu, Xi; Tang, Kefu; Li, Yang; Xiong, Yüting; Shen, Lu; Wei, Zengxin; Zhou, Kejun; Niu, Jiamin; Han, Xuelei; Yang, Lun; Gao, Feng; He, Lin; Qin, Shengying

doi:10.1016/j.parkreldis.2012.04.013

Cited by 35 publications

(33 citation statements)

References 70 publications

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“…The observed OR was similar to the studies of Han Chinese [1,5]. So far, Thai has been the only non-Chinese population, in which the association was demonstrated.…”

Section: Discussionsupporting

confidence: 89%

“…If the genetic factor is involved, transelement rather than cis-element is more likely to alter the p.R1628P genetic effect since in all available data regarding the p.R1628P haplotype to date, all carriers are likely to have the same LRRK2 haplotype [5,6]. The other point is that LRRK2 mutations such as p.G2019S are genetically transmitted with highly age-dependent penetrance [1]. Thus, a long-term study of the asymptomatic carriers of p.R1628P may be helpful to clarify this particular point.…”

Section: Discussionmentioning

confidence: 99%

“…Specific LRRK2 variants often share only one or a few common founders causing carriers of each specific LRRK2 variant to be distributed as a low minor alelle in only particular population [1]. P.G2385R (c.7153G > R; rs34778348) and p.R1628P (c.4883G > C; rs33949390) are the most common variants susceptible for developing to PD in East Asian populations accounting for 3e5% of the population [2e5].…”

Section: Introductionmentioning

confidence: 99%

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Confirmation of the association between LRRK2 R1628P variant and susceptibility to Parkinson's disease in the Thai population

Pulkes

Papsing

Thakkinstian

et al. 2014

Parkinsonism & Related Disorders

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“…The observed OR was similar to the studies of Han Chinese [1,5]. So far, Thai has been the only non-Chinese population, in which the association was demonstrated.…”

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Confirmation of the association between LRRK2 R1628P variant and susceptibility to Parkinson's disease in the Thai population

Pulkes

Papsing

Thakkinstian

et al. 2014

Parkinsonism & Related Disorders

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“…This fi nding has also been replicated, although not as widely as p.G2385R, in various Asian populations including Thai, Taiwanese, and Chinese [ 12 , 45 , 67 , 68 ]. Notably, meta-analysis of all existing studies as of 2012 revealed a consistent risk effect of ~2.5 in typical PD [ 67 ]. In addition, several other exonic variants have been assessed for association with risk for disease, including p.A419V, p.P755L, p.M1646T, and a three-SNP haplotype (p.N551K-p.R1398H-p.K1423K) [ 46 , 67 ].…”

Section: Early Attempts At Finding Risk Locimentioning

confidence: 99%

Genetics of Parkinson’s Disease

Hernandez

Singleton

2015

Movement Disorder Genetics

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Tremendous progress has been made over the last 10 years in the identifi cation of genetic risk factors for Parkinson's disease (PD). This work began with candidate gene-based assessments, where variability in the genes encoding alphasynuclein, glucocerebrosidase, and leucine-rich repeat kinase 2 was assessed and shown to be linked to risk for disease. This work has been considerably extended upon using genome-wide association studies, which have thus far identifi ed a large number of risk loci. Here we discuss these advances, the current picture of genetic risk factors in PD, and the path forward.

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“…Recent studies have also revealed the presence of a variety of other multiple genetic mutations associated with decreased kinase activity as being linked to susceptibility to develop both familial and sporadic Parkinson's disease. [130][131][132] These mutations suppress both auto-phosphorylation as well as phosphorylation of LRRK2 substrates. 133 Because of the structural and functional complexity of LRRK2, the mechanisms by which mutations elicit Parkinsonism are likely to involve multi-interactive signaling systems because variants have been reported to influence mitochondrial function, 134 protein homeostasis, 135 as well as a number of signaling pathways within neurons.…”

Section: Lrrk2mentioning

confidence: 99%

Mutual Neurotoxic Mechanisms Controlling Manganism and Parkisonism

Roth¹

2014

Manganese in Health and Disease

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The studies presented in this review attempt to characterize the functional properties of genes identified as producing Parkinson's disease or Parkinson-like disorders and how mutation of these genes correlate, from a mechanistic perspective, to provocation of manganese (Mn) toxicity. These include genes associated with early-onset of Parkinson's disease, which are comprised of parkin, DJ-1, PINK, and ATP13A2, as well as those associated with late onset of the disorder, which include LRRK2 and VPS35. Because both neurological disorders are associated with altered function and output of the basal ganglia, it is not surprising that symptoms of Parkinson's disease often overlap with that of Mn toxicity. There appears to be four common threads linking the two disorders because mutations in genes associated with early and late onset of Parkinsonism produce similar adverse biological responses acknowledged to provoke Mn-induced dopaminergic cell death: (1) disruption of mitochondrial function leading to oxidative stress; (2) abnormalities in vesicle processing; (3) altered proteasomal and lysosomal protein degradation; and (4) α-synuclein aggregation. The mutual neurotoxic actions of these genes, along with that of Mn, most likely act in synchrony to contribute to the severity, characteristics, and onset of both disorders.

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Quantitative assessment of the effect of LRRK2 exonic variants on the risk of Parkinson’s disease: A meta-analysis

Cited by 35 publications

References 70 publications

Confirmation of the association between LRRK2 R1628P variant and susceptibility to Parkinson's disease in the Thai population

Confirmation of the association between LRRK2 R1628P variant and susceptibility to Parkinson's disease in the Thai population

Genetics of Parkinson’s Disease

Mutual Neurotoxic Mechanisms Controlling Manganism and Parkisonism

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