SNCA variants rs2736990 and rs356220 as risk factors for Parkinson’s disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population

Guo, Xin; Chen, Yong Ping; Song, Wei; Zhao, Bi; Cao, Bei; Wei, Qian; Ou, Ruwei; Yang, Yuan; Li, Yuan; Shang, Huifang

doi:10.1016/j.neurobiolaging.2014.07.014

Cited by 23 publications

(22 citation statements)

References 45 publications

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“…Two independent series of patients were studied. Like our previous study [8], the first cohort of 1055 sporadic PD patients were diagnosed according to the United Kingdom PD Society Brain Bank clinical diagnostic criteria for PD [12]. The second cohort of 320 MSA patients met the current consensus criteria for probable MSA [7].…”

Section: Subjectsmentioning

confidence: 99%

Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population

et al. 2015

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Whether polymorphisms rs11856808 and rs9652490 of the Leucine-rich repeat and Ig domain containing, Nogo receptor-interacting protein-1 (LINGO1) gene, as well as rs10968280, rs13362909 and rs7033345 of the LINGO2 gene, increase the risk for Parkinson's disease (PD) is controversial. Considering the overlap of the clinical and pathological characteristics among PD and multiple system atrophy (MSA), we explored the associations between these five polymorphisms and PD and MSA in a Chinese population. A total of 1055 PD patients, 320 MSA patients, and 810 healthy controls (HCs) were genotyped for these five polymorphisms in LINGO1 and LINGO 2 using Sequenom iPLEX Assay technology. Moreover, after combining our results with available published data, a meta-analysis was conducted to investigate the associations between LINGO 1 rs11856808 and rs9652490 and the risk of PD. The frequency of the minor alleles "T" of LINGO1 rs11856808 was significantly lower in PD than that in HCs (p = 0.011, OR 0.89, 95 % CI 0.81-0.97), but not in MSA. Moreover, there were no significant differences in the minor allele frequency distributions of the other four polymorphisms between PD and HCs, and between MSA and HCs. The meta-analysis showed a lack of association of rs9652490 and PD, regardless of the genetic model or ethnic origin. However, the rs11856808 allele decreased the risk of PD in patients of Asian origin in a dominant genetic model. Our findings suggest that rs11856808 plays a protective role by decreasing the risk for PD, but not for MSA, in Asian population, the other four polymorphisms do not contribute to the risk for PD and MSA.

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Section: Subjectsmentioning

confidence: 99%

Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population

et al. 2015

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“…It is also considered to be a risk factor for these diseases Xiromerisiou et al, 2010). There is evidence of overlapping clinical phenotypes among PD, ALS, and MSA, suggesting that SNCA may confer susceptibility to ALS (Guo et al, 2014). Moreover, pesticides expedite the rate of a-syn fibrillation.…”

Section: Sncamentioning

confidence: 99%

“…Therefore, SNCA may influence the risk of ALS by affecting neuronal toxicity, under combined interaction with pesticides. In total, 5 SNPs across SNCA have been examined, up to now (rs2736990, rs356220, s3775444, rs3822086 and rs11931074) (Guo et al, 2014) producing negative results (Chen et al, 2015;Guo et al, 2014).…”

Section: Sncamentioning

confidence: 99%

Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants

Dardiotis

Siokas

Sokratous

et al. 2018

Environment International

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Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease of the central nervous system, characterized by progressive loss of motor neurons, and occurring in both sporadic and familial form. The origin of the disease is unknown, though increasing evidence suggests that the interaction between genetic and environmental factors may increase susceptibility to ALS, including its sporadic form. Although genetic mutations have been correlated to the familial type of ALS, relatively little is known about the sporadic type (sALS). Genetic factors concerning pesticide metabolism and heavy metal detoxification are increasing the susceptibility to sALS. This review focuses on the genes implicated in metabolic detoxification pathways of environmental toxicants and their potential role in ALS susceptibility.

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“…In a similar fashion, intra-population heterogeneity has also demonstrated to be an important consideration: two snps in SNCA, rs2736990 and rs356220, which have demonstrated to be risk alleles for PD in a Chinese population, failed to show any association with either MSA or amyotrophic lateral scerlosis (ALS) in that same Chinese population. [83] Hence, by performing association studies among several potentially related yet clinically distinct neurodegenerative disorders within a single genetically homogenous population, intra-population heterogeneity may provide clues to the degree of overlap of pathological mechanisms underlying such disorders. Thus, while SNCA loci association studies remain intriguing, replication among and within distinct ethnic groups, in conjunction with whole-genome analysis, will be essential to confirm or reject these associations.…”

Section: What Is Known About the Genetics Of Msamentioning

confidence: 99%

Multiple system atrophy: the application of genetics in understanding etiology

Federoff

Schottlaender²,

Houlden³

et al. 2015

Clin Auton Res

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Classically defined phenotypically by a triad of cerebellar ataxia, parkinsonism and autonomic dysfunction in conjunction with pyramidal signs, multiple system atrophy (MSA) is a rare and progressive neurodegenerative disease affecting an estimated 3-4 per every 100,000 individuals among adults 50-99 years of age. With a pathological hallmark of alpha-synuclein-immunoreactive glial cytoplasmic inclusions (GCIs; Papp-Lantos inclusions), MSA patients exhibit marked neurodegenerative changes in the striatonigral and/or olivopontocerebellar structures of the brain. As a member of the alpha-synucleinopathy family, which is defined by its well-demarcated alpha-synuclein-immunoreactive inclusions and aggregation, MSA’s clinical presentation exhibits several overlapping features with other members including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Given the extensive fund of knowledge regarding the genetic etiology of PD revealed within the past several years, a genetic investigation of MSA is warranted. While a current genome wide association (GWA) study is underway for MSA to further clarify the role of associated genetic loci and single nucleotide polymorphisms (SNPs), several cases have presented solid preliminary evidence of a genetic etiology. Naturally, genes and variants manifesting known associations with PD (and other phenotypically similar neurodegenerative disorders), including SNCA and MAPT, have been comprehensively investigated in MSA patient cohorts. More recently variants in COQ2 have been linked to MSA in the Japanese population although this finding awaits replication. Nonetheless, significant positive associations with subsequent independent replication studies have been scarce. With very limited information regarding genetic mutations or alterations in gene dosage as a cause of MSA, the search for novel risk genes, which may be in the form of common variants or rare variants, is the logical nexus for MSA research. We believe that the application of next generation genetic methods to MSA will provide valuable insight into the underlying causes of this disease, and will be central to the identification of etiologic based therapies.

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SNCA variants rs2736990 and rs356220 as risk factors for Parkinson’s disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population

Cited by 23 publications

References 45 publications

Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population

Analysis and meta-analysis of five polymorphisms of the LINGO1 and LINGO2 genes in Parkinson’s disease and multiple system atrophy in a Chinese population

Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants

Multiple system atrophy: the application of genetics in understanding etiology

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