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

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 as...

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Autores principales:	Megan C. Bakeberg, Madison E. Hoes, Anastazja M. Gorecki, Frances Theunissen, Abigail L. Pfaff, Jade E. Kenna, Kai Plunkett, Sulev Kõks, P. Anthony Akkari, Frank L. Mastaglia, Ryan S. Anderton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9ab3223bbabf470e8f6e3a4036bbd687
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spelling	oai:doaj.org-article:9ab3223bbabf470e8f6e3a4036bbd6872021-12-02T16:30:24ZThe TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease10.1038/s41598-021-85510-02045-2322https://doaj.org/article/9ab3223bbabf470e8f6e3a4036bbd6872021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85510-0https://doaj.org/toc/2045-2322Abstract 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.Megan C. BakebergMadison E. HoesAnastazja M. GoreckiFrances TheunissenAbigail L. PfaffJade E. KennaKai PlunkettSulev KõksP. Anthony AkkariFrank L. MastagliaRyan S. AndertonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megan C. Bakeberg Madison E. Hoes Anastazja M. Gorecki Frances Theunissen Abigail L. Pfaff Jade E. Kenna Kai Plunkett Sulev Kõks P. Anthony Akkari Frank L. Mastaglia Ryan S. Anderton The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
description	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.
format	article
author	Megan C. Bakeberg Madison E. Hoes Anastazja M. Gorecki Frances Theunissen Abigail L. Pfaff Jade E. Kenna Kai Plunkett Sulev Kõks P. Anthony Akkari Frank L. Mastaglia Ryan S. Anderton
author_facet	Megan C. Bakeberg Madison E. Hoes Anastazja M. Gorecki Frances Theunissen Abigail L. Pfaff Jade E. Kenna Kai Plunkett Sulev Kõks P. Anthony Akkari Frank L. Mastaglia Ryan S. Anderton
author_sort	Megan C. Bakeberg
title	The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
title_short	The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
title_full	The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
title_fullStr	The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
title_full_unstemmed	The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease
title_sort	tomm40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9ab3223bbabf470e8f6e3a4036bbd687
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The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

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