Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study

BMC Medical Genetics

Research Article

Lisa F Potts¹  Irene Litvan²  Alex C Cambon³  Shesh N Rai⁴  Ryan J Uitti⁵  Zbigniew K Wszolek⁵  Dennis W Dickson⁶  Rosa Rademakers⁶  Owen A Ross⁶  Matthew J Farrer⁷  David W Hein⁸ 

[1]Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA

[2]Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA

[3]Department of Neurology, University of Louisville, Louisville, KY, USA

[4]Department of Neurosciences, University of California San Diego, La Jolla, CA, USA

[5]Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA

[6]Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA

[7]J.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA

[8]Department of Neurology, Mayo Clinic Jacksonville, Jacksonville, FL, USA

[9]Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA

[10]Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA

[11]Department of Medical Genetics, Centre of Applied Neurogenetics, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

[12]J.G. Brown Cancer Center, University of Louisville, Louisville, KY, USA

[13]Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA

关键词: Progressive supranuclear palsy (PSP);    N;    Tauopathy;    Single nucleotide polymorphisms (SNPs);    Parkinson's disease (PD);   

DOI  :  10.1186/1471-2350-13-16

 received in 2011-09-16, accepted in 2012-03-17,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThere are no known causes for progressive supranuclear palsy (PSP). The microtubule associated protein tau (MAPT) H1 haplotype is the major genetic factor associated with risk of PSP, with both oxidative stress and mitochondrial dysfunction also implicated. We investigated whether specific single nucleotide polymorphisms (SNPs) in genes encoding enzymes of xenobiotic detoxification, mitochondrial functioning, or oxidative stress response, including debrisoquine 4-hydroxylase, paraoxonase 1 and 2, N-acetyltransferase 1 and 2 (NAT2), superoxide dismutase 1 and 2, and PTEN-induced putative kinase are associated with PSP.MethodsDNA from 553 autopsy-confirmed Caucasian PSP cases (266 females, 279 males; age at onset 68 ± 8 years; age at death 75 ± 8) from the Society for PSP Brain Bank and 425 clinical control samples (197 females, 226 males; age at draw 72 ± 11 years) from healthy volunteers were genotyped using Taqman PCR and the SequenomiPLEX Gold assay.ResultsThe proportion of NAT2 rapid acetylators compared to intermediate and slow acetylators was larger in cases than in controls (OR = 1.82, p < 0.05). There were no allelic or genotypic associations with PSP for any other SNPs tested with the exception of MAPT (p < 0.001).ConclusionsOur results show that NAT2 rapid acetylator phenotype is associated with PSP, suggesting that NAT2 may be responsible for activation of a xenobiotic whose metabolite is neurotoxic. Although our results need to be further confirmed in an independent sample, NAT2 acetylation status should be considered in future genetic and epidemiological studies of PSP.

【 授权许可】

Unknown   
© Potts et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.