scholarly journals Polymorphisms of Interleukin-6 and Interleukin-8 Are Not Associated with Parkinson’s Disease in Taiwan

2021 ◽  
Vol 11 (6) ◽  
pp. 768
Author(s):  
Tsai-Wei Liu ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon Chung Fung ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Late Onset ◽  
Age At Onset ◽  
Nucleotide Polymorphisms ◽  
Taiwanese Population ◽  
Negative Results ◽  
Allelic Distribution ◽  
And Gender

Background: Studies have suggested that cytokines are crucial mediators in the pathogenesis of Parkinson’s disease (PD). The multifunctional cytokine interleukin (IL)-6 and its single nucleotide polymorphisms (SNPs) were found to have an impact on the development of PD. However, different studies in associations of IL-6 genetic variants with PD showed inconsistent results and it has never been explored in a Taiwanese population. Both IL-1α and IL-8 contribute to the same inflammation pathway. IL-1α genetic polymorphism has an effect on late-onset PD in Taiwan, whereas the associations of IL-8 genetic variants with PD in Taiwan remain to be investigated. Methods: This study examined the frequencies of polymorphisms within the critical promoter areas of the proinflammatory cytokine genes: IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) in Taiwanese PD patients compared with age-and gender-matched healthy subjects. Comparisons were also made in genotype and allele frequencies of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) among different populations in previous studies. Results: In total, 1120 subjects, including 509 PD patients (female/male: 259/250) and 511 control subjects (female/male: 252/259), were recruited. We found no statistically significant differences in IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) genotypic and allelic distribution between PD and controls, even after being stratified by age at onset and gender. Conclusions: The results did not demonstrate any association of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) with PD in a Taiwanese population. Despite the negative results, this is the first study in associations of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) with PD in Taiwan. The relevance of genetic variants of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) on PD susceptibility warrants further investigation.

scholarly journals Gene4PD: A Comprehensive Genetic Database of Parkinson’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Bin Li ◽  
Guihu Zhao ◽  
Qiao Zhou ◽  
Yali Xie ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Association Studies ◽  
Age At Onset ◽  
Genetic Data ◽  
Genome Wide Association Studies ◽  
Onset Age ◽  
Loss Of Function

Parkinson’s disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30–50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with VPS13C (P = 0.01) was opposite. Finally, we developed an online database named Gene4PD (http://genemed.tech/gene4pd) which integrated published genetic data in PD, the PAGs, and 63 popular genomic data sources, as well as an online pipeline for prioritize risk variants in PD. In conclusion, Gene4PD provides researchers and clinicians comprehensive genetic knowledge and analytic platform for PD, and would also improve the understanding of pathogenesis in PD.

The Evolution of Dementia in Idiopathic Parkinson's Disease: Neuropsychological and Clinical Evidence in Support of Subtypes

1992 ◽  
Vol 4 (4) ◽  
pp. 147-160 ◽  
Author(s):  
Wayne G. J. Reid
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Critical Determinant ◽  
Drug Study ◽  
Baseline Phase ◽  
Onset Group ◽  
Early Onset Group

One hundred and seven newly diagnosed, untreated patients with Parkinson's disease (PD) were divided into two groups according to their age at reported onset of symptoms. Of these, 79 patients were under age 70 (early-onset) and 28 patients were age 70 and over (late-onset). The group of 50 control subjects comprised spouses, friends of the PD patients, and community volunteers. The patients were participants in a multicenter drug study of Parkinson's disease. Each had received a detailed neurological and neuropsychological assessment in the baseline placebo phases of the study. Thirty-4 patients with early-onset and 12 patients with late-onset were reassessed 3 years after treatment with low-dose levodopa, with bromocriptine, or with a combination of the two drugs. The results of the baseline phase of the study revealed that 8% of the early-onset group and 32% of the late-onset group were classified as demented. The 3-year follow-up revealed that the prevalence of dementia had increased to 17% in the early-onset group and to 83% in the late-onset group. This study confirms that at least two distinct subtypes of Parkinson's disease exist. The subtypes differ both clinically and neuropsychologically. The age at onset of symptoms is a critical determinant of the rate and type of cognitive decline in Parkinson's disease.

scholarly journals Rare VPS35 A320V Variant in Taiwanese Parkinson’s Disease Indicates Disrupted CI-MPR Sorting and Impaired Mitochondrial Morphology

2020 ◽  
Vol 10 (11) ◽  
pp. 783
Author(s):  
Yih-Ru Wu ◽  
Chih-Hsin Lin ◽  
Chih-Ying Chao ◽  
Chia-Wen Chang ◽  
Chiung-Mei Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Late Onset ◽  
Mitochondrial Morphology ◽  
Mitofusin 2 ◽  
Ubiquitin Protein Ligase ◽  
Vacuolar Protein ◽  
Cdna Fragments ◽  
Normal Controls

Sequence variants in vacuolar protein sorting 35 (VPS35) have been reported to be associated with Parkinson’s disease (PD). To investigate if the genetic variants in VPS35 contribute to Taiwanese PD, VPS35 cDNA fragments from 62 patients with PD were sequenced. A cohort of PD (n = 560) and ethnically matched controls (n = 506) were further examined for the identified mutation. The effects of the mutation on cation-independent mannose-6-phosphate receptor (CI-MPR) sorting and mitochondrial morphology were further examined in 293T cells expressing the mutant VPS35. Here, a novel heterozygous A320V in the VPS35 gene was identified in two late-onset PD (LOPD) patients, which was absent in 506 normal controls. Expression of the A320V mutant in 293T cells demonstrated increased colocalization of VPS35 with CI-MPR and decreased CI-MPR and lysosomal-associated membrane protein 2 (LAMP2) levels. Decreased CI-MPR manifested in missorting of cathepsin D and decreased proteolysis of α-synuclein. A320V mutation also increased mitochondrial E3 ubiquitin protein ligase 1 (MUL1) and thus led to mitofusin 2 (MFN2) degradation. The results suggest that the expression of VPS35 A320V leads to disrupted CI-MPR sorting and impaired mitochondrial morphology, which may partly explain its action in PD.

Vitamin D receptor genetic variants and Parkinson's disease in a Taiwanese population

2014 ◽  
Vol 35 (5) ◽  
pp. 1212.e11-1212.e13 ◽  
Author(s):  
Chin-Hsien Lin ◽  
Kai-Hsiang Chen ◽  
Meng-Ling Chen ◽  
Han-I. Lin ◽  
Ruey-Meei Wu
Keyword(s):  
Parkinson’S Disease ◽  
Vitamin D ◽  
Parkinson's Disease ◽  
Vitamin D Receptor ◽  
Genetic Variants ◽  
Taiwanese Population

scholarly journals Genetic analysis of Mendelian mutations in a large UK population-based Parkinson’s disease study

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2828-2844 ◽  
Author(s):  
Manuela M X Tan ◽  
Naveed Malek ◽  
Michael A Lawton ◽  
Leon Hubbard ◽  
Alan M Pittman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exome Sequencing ◽  
Clinical Features ◽  
Late Onset ◽  
Age At Onset ◽  
Population Based ◽  
Data Movement ◽  
Young Onset ◽  
Number Of Patients

AbstractOur objective was to define the prevalence and clinical features of genetic Parkinson’s disease in a large UK population-based cohort, the largest multicentre prospective clinico-genetic incident study in the world. We collected demographic data, Movement Disorder Society Unified Parkinson’s Disease Rating Scale scores, and Montreal Cognitive Assessment scores. We analysed mutations in PRKN (parkin), PINK1, LRRK2 and SNCA in relation to age at symptom onset, family history and clinical features. Of the 2262 participants recruited to the Tracking Parkinson’s study, 424 had young-onset Parkinson’s disease (age at onset ≤ 50) and 1799 had late onset Parkinson’s disease. A range of methods were used to genotype 2005 patients: 302 young-onset patients were fully genotyped with multiplex ligation-dependent probe amplification and either Sanger and/or exome sequencing; and 1701 late-onset patients were genotyped with the LRRK2 ‘Kompetitive’ allele-specific polymerase chain reaction assay and/or exome sequencing (two patients had missing age at onset). We identified 29 (1.4%) patients carrying pathogenic mutations. Eighteen patients carried the G2019S or R1441C mutations in LRRK2, and one patient carried a heterozygous duplication in SNCA. In PRKN, we identified patients carrying deletions of exons 1, 4 and 5, and P113Xfs, R275W, G430D and R33X. In PINK1, two patients carried deletions in exon 1 and 5, and the W90Xfs point mutation. Eighteen per cent of patients with age at onset ≤30 and 7.4% of patients from large dominant families carried pathogenic Mendelian gene mutations. Of all young-onset patients, 10 (3.3%) carried biallelic mutations in PRKN or PINK1. Across the whole cohort, 18 patients (0.9%) carried pathogenic LRRK2 mutations and one (0.05%) carried an SNCA duplication. There is a significant burden of LRRK2 G2019S in patients with both apparently sporadic and familial disease. In young-onset patients, dominant and recessive mutations were equally common. There were no differences in clinical features between LRRK2 carriers and non-carriers. However, we did find that PRKN and PINK1 mutation carriers have distinctive clinical features compared to young-onset non-carriers, with more postural symptoms at diagnosis and less cognitive impairment, after adjusting for age and disease duration. This supports the idea that there is a distinct clinical profile of PRKN and PINK1-related Parkinson’s disease. We estimate that there are approaching 1000 patients with a known genetic aetiology in the UK Parkinson’s disease population. A small but significant number of patients carry causal variants in LRRK2, SNCA, PRKN and PINK1 that could potentially be targeted by new therapies, such as LRRK2 inhibitors.

scholarly journals SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease

2019 ◽  
Vol 34 (9) ◽  
pp. 1333-1344 ◽  
Author(s):  
Rubén Fernández‐Santiago ◽  
Núria Martín‐Flores ◽  
Francesca Antonelli ◽  
Catalina Cerquera ◽  
Verónica Moreno ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Nucleotide Polymorphisms ◽  
Age At Onset ◽  
Mtor Pathway ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson’s disease

2014 ◽  
Vol 72 (5) ◽  
pp. 356-359 ◽  
Author(s):  
Hsin Fen Chien ◽  
Tamires Rocha Figueiredo ◽  
Marianna Almeida Hollaender ◽  
Fabiano Tofoli ◽  
Leonel Takao Takada ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Onset ◽  
Small Sample Size ◽  
Clinical Manifestations ◽  
Small Sample ◽  
Genetical Analysis ◽  
G2019s Mutation ◽  
Lrrk2 Gene ◽  
And Gender

Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson’s disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients.Method:We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR).Results:No G2019S mutations were found in both patients with sporadic PD and controls.Conclusions:Our results may be explained by the relatively small sample size.

Genetic Associations With Rapid Motor and Cognitive Deterioration in Parkinson’s Disease

2021 ◽  
Author(s):  
Ling-Xiao Cao ◽  
Yingshan Piao ◽  
Yue Huang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Features ◽  
Brain Aging ◽  
Disease Onset ◽  
Cognitive Deterioration ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Genetic And Environmental Factors ◽  
And Gender

Abstract Background: Parkinson’s disease (PD) is caused by the interplay of genetic and environmental factors during brain aging. About 90 single nucleotide polymorphisms (SNPs) have been recently discovered associating with PD, but their associations with PD clinical features have not been fully characterized yet. Methods: Clinical data of 377 patients with PD who enrolled in Parkinson's Progression Markers Initiative (PPMI) study were obtained. Patients with rapid cognitive or motor progression were determined through clinical assessments over five years follow-up. In addition, genetic information of 50 targeted SNPs was extracted from the genetic database of NeuroX for the same cohort. Genetic associations with rapid motor and cognitive dysfunction of PD were analyzed using SPSS-logistic regression. Results: Among 377 patients with PD, there are more male (31%) than female (17%) prone to have rapid motor progression (p<0.01), who demonstrate 16 points increase in the motor part assessment of MDS-UPDRS. There is no gender difference in rapid cognitive deterioration. Four SNPs (rs11724635, rs12528068, rs591323, rs17649553) were associated with fast cognitive decline (p<0.05) and the extended 50 SNPs researches excellent predicative value of area under curve (AUC) at 0.961. Three SNPs (rs823118, rs10797576, rs12456492) were associated with faster motor progression (p<0.05), and the extended 50 SNPs and gender researches fair prediction of AUC at 0.736. There were multiple genetic associations with initial clinical presentations of PD at baseline as well. Conclusions: Genetic factors contribute to the disease progression as well as the clinical features at the disease onset.

scholarly journals Association between CSF1 and CSF1R Polymorphisms and Parkinson’s Disease in Taiwan

2019 ◽  
Vol 8 (10) ◽  
pp. 1529 ◽  
Author(s):  
Kuo-Hsuan Chang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hsiu-Chuan Wu ◽  
Chiung-Mei Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Age At Onset ◽  
Genetic Associations ◽  
Age And Gender ◽  
Control Subjects ◽  
Important Pathway ◽  
And Gender ◽  
And Control ◽  
First Time

Background: CSF1/CSF1R neuroinflammatory signaling is emerging as an important pathway involved in the pathogenesis of Parkinson’s disease (PD). However, the genetic associations between CSF1/CSF1R and PD have not yet been explored. Methods: We investigated the effects of two functional genetic variants, including CSF1 rs1058885 and CSF1R rs10079250 in a cohort including 502 Taiwanese patients with PD and 511 age- and gender-matched healthy controls. Results: The CSF1 rs1058885 TT genotype was less frequent in PD patients compared with control subjects (odds ratio (OR) = 0.63, 95% confidence interval (CI): 0.43–0.92, p = 0.015). The PD patients also had a lower frequency of the CSF1 rs1058885 T allele compared with the control subjects (OR = 0.80, 95% CI: 0.67–0.96, p = 0.014). No statistically significant differences in allelic and genotypic frequencies of CSF1R rs10079250 between the PD and control subjects were found, even after stratification by age at onset and gender. Conclusion: This study reports a genetic association between CSF1 and PD for the first time.

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