Mitochondrial transcription factor A variants and the risk of Parkinson's disease.
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.
Gaweda-Walerych
Katarzyna
K
Department of Neurodegenerative Disorders, Medical Research Center, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland. kabgaweda@poczta.onet.pl
Safranow
Krzysztof
K
Maruszak
Aleksandra
A
Bialecka
Monika
M
Klodowska-Duda
Gabriela
G
Czyzewski
Krzysztof
K
Slawek
Jaroslaw
J
Rudzinska
Monika
M
Styczynska
Maria
M
Opala
Grzegorz
G
Drozdzik
Marek
M
Kurzawski
Maciej
M
Szczudlik
Andrzej
A
Canter
Jeffrey A
JA
Barcikowska
Maria
M
Zekanowski
Cezary
C
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
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A