Mitochondrial transcription factor A variants and the risk of Parkinson's disease
2009; Elsevier BV; Volume: 469; Issue: 1 Linguagem: Inglês
10.1016/j.neulet.2009.11.037
ISSN1872-7972
AutoresKatarzyna Gaweda‐Walerych, Krzysztof Safranow, Aleksandra Maruszak, Monika Białecka, Gabriela Kłodowska-Duda, K Czyźewski, Jarosław Sławek, Monika Rudzińska, Maria Styczyńska, Grzegorz Opala, Marek Droździk, Maciej Kurzawski, Andrzej Szczudlik, Jeffrey A. Canter, Maria Barcikowska, Cezary Żekanowski,
Tópico(s)Metabolism and Genetic Disorders
ResumoThe 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 (χ2 4.523, p = 0.0334). Conversely, four of five haplotypes containing allele G had higher frequencies in PD group, with no statistical significance.
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