Document Detail


Mitochondrial transcription factor A variants and the risk of Parkinson's disease.
MedLine Citation:
PMID:  19925850     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mitochondrial transcription factor A (TFAM) has been recently shown to decrease reactive oxygen species (ROS) generation. It is also known that mitochondrial DNA (mtDNA) haplogroups might confer different coupling properties, resulting in different ROS levels. We hypothesized that potentially functional TFAM variants could influence PD risk depending on haplogroup background. To test this we assessed the role of six TFAM variants on PD risk in 326 PD patients and 316 controls, and correlated it with mtDNA haplogroup clusters (HV, JTKU and a putative functionally different group U4U5a1KJ1cJ2, connected previously with partial uncoupling of oxidative phosphorylation). Both genotype and haplotype analysis showed that intronic variant rs2306604 modifies PD risk. Multivariate logistic regression analysis confirmed that rs2306604 G/G genotype is an independent risk factor for PD (OR 1.789, 95% CI 1.162-2.755, p=0.008). There was a borderline interaction between G/G genotype and HV haplogroup (p=0.075). Haplotype analysis showed that all three haplotypes containing rs2306604 allele A occurred at higher frequencies in controls, but only one of them reached statistical significance (chi(2) 4.523, p=0.0334). Conversely, four of five haplotypes containing allele G had higher frequencies in PD group, with no statistical significance.
Authors:
Katarzyna Gaweda-Walerych; Krzysztof Safranow; Aleksandra Maruszak; Monika Bialecka; Gabriela Klodowska-Duda; Krzysztof Czyzewski; Jaroslaw Slawek; Monika Rudzinska; Maria Styczynska; Grzegorz Opala; Marek Drozdzik; Maciej Kurzawski; Andrzej Szczudlik; Jeffrey A Canter; Maria Barcikowska; Cezary Zekanowski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-17
Journal Detail:
Title:  Neuroscience letters     Volume:  469     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  24-9     Citation Subset:  IM    
Copyright Information:
(c) 2009 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. kabgaweda@poczta.onet.pl
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
DNA-Binding Proteins / genetics*
Female
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Haplotypes
Humans
Linkage Disequilibrium
Male
Middle Aged
Mitochondrial Proteins / genetics*
Multigene Family
Oxidative Phosphorylation
Parkinson Disease / genetics*
Risk
Transcription Factors / genetics*
Young Adult
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Mitochondrial Proteins; 0/Transcription Factors; 0/mitochondrial transcription factor A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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