Bakeberg, Megan C, Hoes, Madison E, Gorecki, Anastazja M, Theunissen, Frances, Pfaff, Abigail L, Kenna, Jade E, Plunkett, Kai, Koks, Sulev 
ORCID: 0000-0001-6087-6643, Akkari, P Anthony, Mastaglia, Frank L et al (show 1 more authors)
(2021)
The <i>TOMM40 '523'</i> polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson's disease.
SCIENTIFIC REPORTS, 11 (1).
6363-.
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The TOMM40 523 polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinsons disease.pdf - Published version Download (1MB) | Preview |
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 '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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mitochondria, Humans, Parkinson Disease, Alzheimer Disease, Genetic Predisposition to Disease, Apolipoproteins E, Membrane Transport Proteins, Risk Factors, Cohort Studies, Age of Onset, Gene Frequency, Polymorphism, Genetic, Aged, Middle Aged, Australia, Female, Male, Mitochondrial Membranes, Genetic Association Studies, Cognitive Dysfunction, Mitochondrial Precursor Protein Import Complex Proteins |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Mar 2021 15:06 |
| Last Modified: | 19 Oct 2023 08:43 |
| DOI: | 10.1038/s41598-021-85510-0 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3118240 |
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