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

Li, Kai; Tang, Beisha; Liu, Zhenhua; Kang, Ji-feng; Zhang, Yuan; Shen, Lu; Li, Nan; Yan, Xinxiang; Xia, Kun; Guo, Jifeng

doi:10.1016/j.neurobiolaging.2015.07.012

Cited by 20 publications

(14 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…e MAF for p.Ala419Val in PD patients in our study was 0.02, which is higher than in Chinese and Taiwanese populations and closer to Japanese and Korean (Table 7). Taking into account the young mean AAO in our Kazakhstani PD cohort (55.06 ± 11.15) and reference to Li et al [26], one might explain the high MAF for p.Ala419Val. Moreover, the AAO in p.Ala419Val-positive PD patients was remarkably young (48.3 ± 12.6) in our study.…”

Section: Pala419valmentioning

confidence: 54%

“…is has been explained by possible natural sampling variation and population heterogeneity [30] on the one hand. [26] argued that the discrepancy is likely to result from different mean ages at onset (AAO) of PD patients in these studies. us, while the mean AAO in p.Ala419Val-positive reports on Chinese ethnicity was <55 years [23,26,29], negative reports on the same population had AAO above 60 years [28,30,31,33].…”

Section: Pala419valmentioning

confidence: 88%

“…[26] argued that the discrepancy is likely to result from different mean ages at onset (AAO) of PD patients in these studies. us, while the mean AAO in p.Ala419Val-positive reports on Chinese ethnicity was <55 years [23,26,29], negative reports on the same population had AAO above 60 years [28,30,31,33]. Provided the fact that p.Ala419Val might have a strong association with earlyonset Chinese PD, the likelihood of yielding positive findings could be higher in young-onset PD cohorts.…”

Section: Pala419valmentioning

confidence: 88%

“…Interestingly, the replication studies in the Chinese and Taiwanese ethnicities have yielded inconsistent results. While p.Ala419Val was negative or positive with insignificant OR in some studies, several studies and their metaanalysis reported a significant association between this variant and predominantly early-onset PD ( Table 7, [26]). is has been explained by possible natural sampling variation and population heterogeneity [30] on the one hand.…”

Section: Pala419valmentioning

confidence: 98%

“…ere have been nine reports describing p.Ala419Val variant [26]. e variant resides in the LRRK2 Armadillo domain and is predicted deleterious by online prediction tools with high conservation in the vertebrates [26].…”

Section: Pala419valmentioning

confidence: 99%

See 4 more Smart Citations

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

Kaiyrzhanov

Aitkulova

Shashkin

et al. 2020

Parkinson's Disease

View full text Add to dashboard Cite

Background. LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. Objective. Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort. Methods. 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis. Results. None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, p=0.8), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, p=0.4), and p.Arg1628Pro was found only in 1% of controls. p.Gly2385Arg was positive in a big family with PD and tremor, although with incomplete segregation. One early-onset PD subject was homozygous for p.Ala419Val who developed fast progression and severe dyskinesias. p.Ala419Val was associated with early-onset PD. Conclusions. We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts.

show abstract

Section: Pala419valmentioning

confidence: 54%

Section: Pala419valmentioning

confidence: 88%

Section: Pala419valmentioning

confidence: 88%

Section: Pala419valmentioning

confidence: 98%

Section: Pala419valmentioning

confidence: 99%

See 3 more Smart Citations

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

Kaiyrzhanov

Aitkulova

Shashkin

et al. 2020

Parkinson's Disease

View full text Add to dashboard Cite

show abstract

Analysis of rare variants of autosomal‐dominant genes in a Chinese population with sporadic Parkinson’s disease

Zheng

Jin

Chen

et al. 2020

Molec Gen & Gen Med

View full text Add to dashboard Cite

Parkinson's disease (PD) is the most common movement disorder (Alves, Forsaa, Pedersen, Dreetz Gjerstad, & Larsen, 2008), with a global prevalence of 6.2 million cases in 2015 that is estimated to rise to 12.9 million by 2040 (Dorsey & Bloem, 2018). PD is defined by two major neuropathological hallmarks: loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain and the presence of Lewy bodies (LB) (Postuma et al., 2015). However, the etiology of

show abstract

A glimpse of the genetics of young‐onset Parkinson’s disease in Central Asia

Kaiyrzhanov

Aitkulova

Vandrovcová

et al. 2021

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

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

Cited by 20 publications

References 21 publications

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

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

Analysis of rare variants of autosomal‐dominant genes in a Chinese population with sporadic Parkinson’s disease

A glimpse of the genetics of young‐onset Parkinson’s disease in Central Asia

Contact Info

Product

Resources

About