SNCAGene, but NotMAPT, Influences Onset Age of Parkinson’s Disease in Chinese and Australians

Background.α-Synuclein (SNCA) and microtubule-associated protein tau (MAPT) are the two major genes independently, but not jointly, associated with susceptibility for Parkinson’s disease (PD). TheSNCAgene has recently been identified as a major modifier of age of PD onset. WhetherMAPTgene synergistically influences age of onset of PD is unknown.Objective. To investigate independent and joint effects ofMAPTandSNCAon PD onset age.Methods. 412 patients with PD were recruited from the Australian PD Research Network (123) and the Neurology Department, Ruijin Hospital Affiliated to Shanghai Jiaotong University, China (289).MAPT(rs17650901) tagging H1/H2 haplotype andSNCA(Rep1) were genotyped in the Australian cohort, andMAPT(rs242557, rs3744456) andSNCA(rs11931074, rs894278) were genotyped in the Chinese cohort. SPSS regression analysis was used to test genetic effects on age at onset of PD in each cohort.Results.SNCApolymorphisms associated with the onset age of PD in both populations.MAPTpolymorphisms did not enhance such association in either entire cohort.Conclusion. This study suggests that, in both ethnic groups,SNCAgene variants influence the age at onset of PD andα-synuclein plays a key role in the disease course of PD.

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The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-85510-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Megan C. Bakeberg ◽

Madison E. Hoes ◽

Anastazja M. Gorecki ◽

Frances Theunissen ◽

Abigail L. Pfaff ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Disease Risk ◽

Age Of Onset ◽

Sequencing Analysis ◽

Age Related ◽

Australian Cohort ◽

Progression Markers ◽

Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

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Gene4PD: A Comprehensive Genetic Database of Parkinson’s Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.679568 ◽

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.

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The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease.

10.21203/rs.3.rs-119345/v1 ◽

2020 ◽

Author(s):

Megan Bakeberg ◽

Madison Hoes ◽

Anastazja Gorecki ◽

Frances Theunissen ◽

Abigail Pfaff ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Symptom Onset ◽

Disease Risk ◽

Age Of Onset ◽

Sequencing Analysis ◽

Age Related ◽

Australian Cohort ◽

Progression Markers ◽

Age Related Cognitive Decline

Abstract Abnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not in the Australian cohort. Variation in the TOMM40 structural variant was not associated with PD risk, but may be a modifying factor for age of symptom onset in some PD populations, warranting further investigation.

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Pink1 type of Early Onset Parkinson’s disease(EOPD)in Sudanese patients, 2018

Sudan Journal of Medical Sciences ◽

10.18502/sjms.v14i3.5207 ◽

2019 ◽

Author(s):

Etedal Ahmed A. Ibrahim ◽

Samer Abdalaziz Albasher

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Early Onset ◽

Age Of Onset ◽

Age At Onset ◽

Age Group ◽

Pink1 Gene ◽

The Mean ◽

Early Onset Parkinson’S Disease

Background: Parkinson’sDisease (PD) is a neurodegenerative disorder affecting the motor system. It is a chronic progressive disorder which leads to long standing disability. Objective: To study the Presentations and pink1 gene in young Sudanese patients with Parkinson’s disease . Material and Methods: A prospective study was conducted among 31 PD patients at the National center for Neurological Science (NCNS) at Khartoum state. A structured questionnaire was used for data collection. Consisted of personal data, clinical presentations and investigations. RT-PCR technique using G-spin™ kit. PINK1 gene was detected in most of the samples it was strongly positive. The data was analyzed using SPSS version 21. Results:. The majority of them 19 (61%) were located in age group 41 – 50 years; the mean age of onset was 33.4+_12 yrs. 19 (61%) of the subjects were males and 12 (39%) were female with ratio 1.6:1 (M: F), 20 (64.5%) were married. , 8 (40%) were endogamous married. 5 (62.5%) were second degree and 3 (37.5%) were third degree. 17 (85%) had children, 2 (10%) of the patient had children with Parkinson’s disease. 22 (71%) had duration more than 12 months, 12 (39%) age more than 40 years. 29 (93.5%) had tremor, 27 (87.1%) had rigidity and 23 (74.2%) had bradykinesia. 14 (45%) had positive family history of Parkinson’s disease. PINK1 gene expression was detected in 28 (90.3%) of the patients. no significant associations were found between PINK1 expression with age, gender, age at onset and family history (P> 0.05). Conclusion: This study concludes that early onset PD was common among male than female. The most affected age group was found to be 41 – 50 years and the mean age of onset 33.4yrs. Also, the patterns of the clinical features were generally similar to literature. PINK1 expression was predominant with no significant associations were found between PINK1 expression with age, gender, age at onset and family history. Key words: , Early onset,, Parkinson’s disease, Pink1 gene, Sudan.

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Role of the Long Non-Coding RNA MAPT-AS1 in Regulation of Microtubule Associated Protein Tau (MAPT) Expression in Parkinson's Disease

PLoS ONE ◽

10.1371/journal.pone.0157924 ◽

2016 ◽

Vol 11 (6) ◽

pp. e0157924 ◽

Cited By ~ 26

Author(s):

Kirsten G. Coupland ◽

Woojin S. Kim ◽

Glenda M. Halliday ◽

Marianne Hallupp ◽

Carol Dobson-Stone ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Tau ◽

Microtubule Associated Protein Tau ◽

Non Coding Rna ◽

Long Non Coding Rna

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A voxel-based PET study of dopamine transporters in Parkinson's disease: Relevance of age at onset

Neurobiology of Disease ◽

10.1016/j.nbd.2008.03.012 ◽

2008 ◽

Vol 31 (1) ◽

pp. 102-109 ◽

Cited By ~ 21

Author(s):

Andrea Panzacchi ◽

Rosa Maria Moresco ◽

Valentina Garibotto ◽

Angelo Antonini ◽

Clara Gobbo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Age At Onset ◽

Dopamine Transporters ◽

Disease Relevance

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FAKTOR-FAKTOR YANG MEMPENGARUHI SUBTIPE GEJALA MOTORIK PENYAKIT PARKINSON

Human Care Journal ◽

10.32883/hcj.v5i1.649 ◽

2020 ◽

Vol 5 (1) ◽

pp. 343

Author(s):

Attiya Istarini ◽

Yuliarni Syafrita ◽

Restu Susanti

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Age At Onset ◽

Motor Symptom ◽

Disease Stage ◽

Motor Symptoms ◽

Research Subjects ◽

Cross Sectional ◽

Duration Of Disease ◽

Cross Sectional Design

Background: Parkinson's disease (PD) is a chronic neurodegenerative disease that manifests as movement disorders. Based on motor symptoms, PD is classified into subtypes of tremor and postural instability gait disorders (PIGD). The motor symptoms subtype is a predictor of disease progression, therapeutic response, and quality of life for Parkinson's patients. The purpose of this study is to identify some factors that influence motor symptoms in Parkinson's disease.Methods: This research use cross sectional design. Samples were selected by consecutive sampling method that met the inclusion and exclusion criteria. Research subjects were 58 people. Statistical analysis using SPSS. p values <0.05 were considered statistically significant.Results: This research include 58 patients, 55.2% were men with range of age 63.5 ± 8.5 years old. The mean age at onset was 57.9 ± 9.5 years and duration of disease 6.1 ± 4.6 years. Motor symptoms 53.4% dominant tremor. There was a significant relationship between disease stage and motor symptom subtypes (p <0.001). There is no relationship between the patient's age, age at onset and duration of the disease with motor symptom subtypes.Conclusions: There is a relationship between disease stage and motor symptom. The patient's age, age at onset and duration of the disease are not related to the motor symptoms of Parkinson's patients.

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Study of The Collagen Type VI Alpha 3 (COL6A3) Gene in Parkinson’s Disease

10.21203/rs.3.rs-210101/v1 ◽

2021 ◽

Author(s):

Chong-Yao Jin ◽

Ran Zheng ◽

Zhi-Hao Lin ◽

Nai-Jia Xue ◽

Ying Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Collagen Type ◽

Gene Mutations ◽

Compound Heterozygous ◽

Genetic Characteristics ◽

Increased Risk ◽

Collagen Type Vi ◽

Chinese Cohort ◽

Aggregate Burden

Abstract Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of < 0.01; and 2) the variant being recognized as deleterious by at least 15 different in silico predicting tools. Finally, we tested the aggregate burden of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified seven novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.03). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

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Cognitive Influences in Parkinson's Disease Patients and Their Caregivers: Perspectives From an Australian Cohort

Frontiers in Neurology ◽

10.3389/fneur.2021.673816 ◽

2021 ◽

Vol 12 ◽

Author(s):

Michal Lubomski ◽

Ryan L. Davis ◽

Carolyn M. Sue

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Impairment ◽

Cognitive Influences ◽

Lower Education Level ◽

Caregiver Quality ◽

Australian Cohort ◽

Lower Education ◽

Non Motor Symptoms

Objectives: Cognitive impairment impacts negatively on Parkinson's disease (PD) patient and caregiver quality of life (QoL). We examined cognitive impairment in PD patients and their caregivers to determine if caregiver cognition affected their PD relative.Methods: Validated cognition and clinical outcome measures were assessed in 103 PD patients and 81 caregivers.Results: PD patients showed more cognitive impairment than their carers, with 48.6% having possible Mild Cognitive Impairment (MCI) and 16.5% having PD dementia. Increasing age, male gender, lower education level, various non-motor symptoms and certain therapies, associated with poorer cognition in PD. Eighteen and a half percent of caregivers were found to have MCI, in association with a lower physical and mental QoL. This reflected in lower QoL and mood for the respective PD patients.Conclusion: Impaired cognition and QoL in caregivers was associated with decreased QoL and mood for respective PD patients, suggesting MCI in caregivers is an important consideration for the management of PD.

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