Mitochondrial transcription factor A variants and the risk of Parkinson's disease

• Published in: Neuroscience letters 2010-01, Vol.469 (1), p.24-29
• Main Authors: Gaweda-Walerych, Katarzyna, Safranow, Krzysztof, Maruszak, Aleksandra, Bialecka, Monika, Klodowska-Duda, Gabriela, Czyzewski, Krzysztof, Slawek, Jaroslaw, Rudzinska, Monika, Styczynska, Maria, Opala, Grzegorz, Drozdzik, Marek, Kurzawski, Maciej, Szczudlik, Andrzej, Canter, Jeffrey A., Barcikowska, Maria, Zekanowski, Cezary
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA-Binding Proteins - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Mitochondrial haplogroup clusters; Mitochondrial Proteins - genetics; Multigene Family; Neurology; Oxidative Phosphorylation; Parkinson Disease - genetics; Parkinson's disease; Risk; TFAM; Transcription Factors - genetics; Vertebrates: nervous system and sense organs; Young Adult
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.11.037

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 (χ2 4.523, p=0.0334). Conversely, four of five haplotypes containing allele G had higher frequencies in PD group, with no statistical significance.