Familial genes in sporadic disease: Common variants of α-synuclein gene associate with Parkinson's disease

Owen A. Ross; David Gosal; Jeremy T. Stone; Sarah J. Lincoln; Michael G. Heckman; G. Brent Irvine; Janet A. Johnston; J. Mark Gibson; Matthew J. Farrer; Timothy Lynch

doi:10.1016/j.mad.2007.04.002

Familial genes in sporadic disease: Common variants of α-synuclein gene associate with Parkinson's disease

Owen A. Ross, David Gosal, Jeremy T. Stone, Sarah J. Lincoln, Michael G. Heckman, G. Brent Irvine, Janet A. Johnston, J. Mark Gibson, Matthew J. Farrer, Timothy Lynch

Neuroscience

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Genetic variation of the α-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3′UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.

Original language	English (US)
Pages (from-to)	378-382
Number of pages	5
Journal	Mechanisms of Ageing and Development
Volume	128
Issue number	5-6
DOIs	https://doi.org/10.1016/j.mad.2007.04.002
State	Published - May 2007

Keywords

Parkinson's disease
Polymorphism
α-Synuclein

ASJC Scopus subject areas

Aging
Developmental Biology

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10.1016/j.mad.2007.04.002

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title = "Familial genes in sporadic disease: Common variants of α-synuclein gene associate with Parkinson's disease",

abstract = "Genetic variation of the α-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3′UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.",

keywords = "Parkinson's disease, Polymorphism, α-Synuclein",

author = "Ross, {Owen A.} and David Gosal and Stone, {Jeremy T.} and Lincoln, {Sarah J.} and Heckman, {Michael G.} and Irvine, {G. Brent} and Johnston, {Janet A.} and Gibson, {J. Mark} and Farrer, {Matthew J.} and Timothy Lynch",

note = "Funding Information: We are grateful to the following organizations for their support of this work: The R&D Office of the Health and Personal Social Services and the Department of Employment and Learning (Northern Ireland). The Republic of Ireland research consortium was supported by a Programme for Research in Third-Level Institutions (PRTLI) neurosciences award. We would like to thank Minnie Schreiber for laboratory support, our research nurse Paula Woods of the Neurology department in the City Hospital, Belfast. Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS40256). We would like to thank all those who have contributed to our research, particularly the patients and their families.",

year = "2007",

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doi = "10.1016/j.mad.2007.04.002",

language = "English (US)",

volume = "128",

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journal = "Mechanisms of Ageing and Development",

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T2 - Common variants of α-synuclein gene associate with Parkinson's disease

AU - Ross, Owen A.

AU - Gosal, David

AU - Stone, Jeremy T.

AU - Lincoln, Sarah J.

AU - Heckman, Michael G.

AU - Irvine, G. Brent

AU - Johnston, Janet A.

AU - Gibson, J. Mark

AU - Farrer, Matthew J.

AU - Lynch, Timothy

N1 - Funding Information: We are grateful to the following organizations for their support of this work: The R&D Office of the Health and Personal Social Services and the Department of Employment and Learning (Northern Ireland). The Republic of Ireland research consortium was supported by a Programme for Research in Third-Level Institutions (PRTLI) neurosciences award. We would like to thank Minnie Schreiber for laboratory support, our research nurse Paula Woods of the Neurology department in the City Hospital, Belfast. Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS40256). We would like to thank all those who have contributed to our research, particularly the patients and their families.

PY - 2007/5

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N2 - Genetic variation of the α-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3′UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.

AB - Genetic variation of the α-synuclein gene (SNCA) is known to cause familial parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease (PD) remains elusive. The present study identifies an association of common SNCA polymorphisms with disease susceptibility in a series of Irish PD patients. There is evidence for association with alternate regions, of protection and risk which may act independently/synergistically, within the promoter region (Rep1; OR: 0.59, 95% CI: 0.37-0.84) and the 3′UTR of the gene (rs356165; OR: 1.67, 95% CI: 1.08-2.58). Given previous reports of association a collaborative effort is required which may exploit global linkage disequilibrium patterns for SNCA and standardise polymorphic markers used in each population. It is now crucial to identify the susceptibility allele and elucidate its functionality which may generate a therapeutic target for PD.

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Familial genes in sporadic disease: Common variants of α-synuclein gene associate with Parkinson's disease

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