Case control analysis of LRRK2 Gly2385Arg in Alzheimer's disease

Tan, Eng King; Lee, J.; Chen, C.P.; Wong, Michael; Zhao, Yongxiang

doi:10.1016/j.neurobiolaging.2007.07.010

Cited by 16 publications

(10 citation statements)

References 5 publications

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“…Although the exact changes in function after substitution of glycine to arginine is still unknown, it is certain that the variant leads to cell death and apoptosis under oxidative stress in vitro [18]. In another common neurodegenerative disease, Alzheimer’s disease, this variant does not appear to modulate its risk [29]. That was coincident with one study on the association of multiple system atrophy with LRRK2 p. 2019G>S in the United States [28].…”

Section: Discussionmentioning

confidence: 99%

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

Peng

et al. 2008

Euro J of Neurology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Peng

et al. 2008

Euro J of Neurology

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“…Moreover, it has been noted that in patients with the Y1699C and R1441C mutations, degeneration is not solely restricted to dopaminergic neurons of the SNpc, however, PET scan analysis indicated that the in vivo phenotype associated with these two mutations is indistinguishable from that of sporadic PD despite the pathological heterogeneity (Adams et al 2005). Interestingly, mutations in LRRK2 have not been found in other primary neurodegenerative diseases such as Alzheimer’s disease (AD), PSP, or frontotemporal dementia (FTD) (Hernandez D 2005; Tan et al 2007a; Toft et al 2005). The diverse pathologies associated with LRRK2 mutations strongly suggest that this protein may be involved in multiple cellular processes in neurons.…”

Section: Prevalence and Pathological Features Of Lrrk2 Disease-associmentioning

confidence: 99%

Leucine‐rich repeat kinase 2 (LRRK2): A key player in the pathogenesis of Parkinson's disease

Gandhi

Chen

Wilson-Delfosse

2008

J of Neuroscience Research

112

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Parkinson’s disease (PD) is the most common neurodegenerative movement disorder with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have recently been linked to autosomal dominant, late-onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multi-domain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease-associated mutations are found throughout the multi-domain structure of the protein. LRRK2, however, is unique among the PD-causing genes because a missense mutation, G2019S, is a frequent determinant of not only familial, but also of sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. This article reviews the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2.

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“…As the Asian continent is large with diverse ethnic backgrounds, more scientific studies are still needed to determine if the variant is race‐specific. The variant thus far has not associated with other neurodegenerative diseases [21].…”

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confidence: 99%