title: Mitochondrial transcription factor A variants and the risk of Parkinson's disease.
abstract: 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.affiliation: Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. kabgaweda@poczta.onet.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gaweda-Walerych
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Safranow
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Maruszak
authors.forename: Monika
authors.initials: M
authors.lastname: Bialecka
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klodowska-Duda
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czyzewski
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Slawek
authors.forename: Monika
authors.initials: M
authors.lastname: Rudzinska
authors.forename: Maria
authors.initials: M
authors.lastname: Styczynska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opala
authors.forename: Marek
authors.initials: M
authors.lastname: Drozdzik
authors.forename: Maciej
authors.initials: M
authors.lastname: Kurzawski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczudlik
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Canter
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D005810:Multigene Family; D010085:Oxidative Phosphorylation; D010300:Parkinson Disease / Q000235:genetics*; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A