A novel screen for nuclear mitochondrial gene associations with Parkinson?s disease (original) (raw)
Abstract
Genetic factors play an important role in the aetiology of Parkinson's disease (PD). We have screened nuclear genes encoding subunits of mitochondrial complex I for associations between single nucleotide polymorphisms (SNPs) and PD. Abnormal functioning of complex I is well documented in human PD. Moreover, toxicological inhibition of complex I can lead to parkinsonism in animals. Thus, commonly occurring variants in these genes could potentially influence complex I function and the risk of developing PD. A subset of 70 potential SNPs in 31 nuclear complex I genes were selected and association analysis was performed on 306 PD patients plus 321 unaffected control subjects. Genotyping was performed using the DASH method. There was no evidence that the examined SNPs were significant genetic risk factors for PD, although this initial screen could not exclude the possibility that other disease-influencing variations exist within these genes.
Loading Preview
Sorry, preview is currently unavailable. You can download the paper by clicking the button above.
References (25)
- Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 3(12): 1301-1306
- Calne DB, Snow BJ, Lee C (1992) Criteria for diagnosing Parkinson's disease. Ann Neurol 32 [Suppl]: S125-S127
- de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, Fratiglioni L, Lobo A, Martinez-Lage J, Trenkwalder C, Hofman A (2000) Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54(11): S21-S23
- Emahazion T, Feuk L, Jobs M, Sawyer SL, Fredman D, St Clair D, Prince JA, Brookes AJ (2001) SNP association studies in Alzheimer's disease highlight problems for complex disease analysis. Trends Genet 17(7): 407-413
- Fredman D, Siegfried M, Yuan YP, Bork P, Lehvaslaiho H, Brookes AJ (2002) HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources. Nucl Acids Res 30(1): 387-391
- Gu M, Cooper JM, Taanman JW, Schapira AH (1998) Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease. Ann Neurol 44(2): 177-186
- Hattori N, Yoshino H, Tanaka M, Suzuki H, Mizuno Y (1998) Genotype in the 24-kDa subunit gene (NDUFV2) of mitochondrial complex I and susceptibility to Parkinson disease. Genomics 49(1): 52-58
- Howell WM, Jobs M, Gyllensten U, Brookes AJ (1999) Dynamic allele-specific hybridization. A new method for scoring single nucleotide polymorphisms. Nat Biotechnol 17(1): 87-88
- Le Couteur DG, Muller M, Yang MC, Mellick GD, McLean AJ (2002) Aging-environment and gene-environment interactions in the pathogenesis of Parkinson's disease. Rev Environ- mental Health 17(1): 51-64
- Matsushita S, Arai H, Yuzuriha T, Kato M, Matsui T, Urakami K, Higuchi S (2001) No association between DLST gene and Alzheimer's disease or Wernicke-Korsakoff syndrome. Neurobiol Aging 22(4): 569-574
- Mizuno Y, Yoshino H, Ikebe S, Hattori N, Kobayashi T, Shimoda-Matsubayashi S, Matsumine H, Kondo T (1998) Mitochondrial dysfunction in Parkinson's disease. Ann Neurol 44[3 Suppl 1]: S99-S109
- Mouradian MM (2002) Recent advances in the genetics and pathogenesis of Parkinson disease. Neurology 58(2): 179-185
- G. D. Mellick et al.
- Nakano K, Ohta S, Nishimaki K, Miki T, Matuda S (1997) Alzheimer's disease and DLST genotype. Lancet 350(9088): 1367-1368
- Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4- phenyl-1,2,5,6-tetrahydropyridine. Life Sci 36(26): 2503-2508
- Prince JA, Feuk L, Howell WM, Jobs M, Emahazion T, Blennow K, Brookes AJ (2001) Robust and accurate single nucleotide polymorphism genotyping by dynamic allele-specific hybri- dization (DASH): design criteria and assay validation. Genome Res 11(1): 152-162
- Schapira AH (1994) Evidence for mitochondrial dysfunction in Parkinson's disease -a critical appraisal. Mov 9(2): 125-138
- Sheu KF, Brown AM, Kristal BS, Kalaria RN, Lilius L, Lannfelt L, Blass JP (1999) A DLST genotype associated with reduced risk for Alzheimer's disease. Neurology 52(7): 1505-1507
- Smeitink J, van den Heuvel L (1999) Human mitochondrial complex I in health and disease. Am J Hum Genet 64(6): 1505-1510
- Smeitink J, van den Heuvel L, DiMauro S (2001) The genetics and pathology of oxidative phosphorylation. Nat Rev Genet 2(5): 342-352
- Sveinbjornsdottir S, Hicks AA, Jonsson T, Petursson H, Gugmundsson G, Frigge ML, Kong A, Gulcher JR, Stefansson K (2000) Familial aggregation of Parkinson's disease in Iceland. N Engl J Med 343(24): 1765-1770
- Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, Bennett JP Jr, Davis RE, Parker WD Jr (1996) Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol 40(4): 663-671
- Vives-Bauza C, Andreu AL, Manfredi G, Beal MF, Janetzky B, Gruenewald TH, Lin MT (2002) Sequence analysis of the entire mitochondrial genome in Parkinson's disease. Biochem Biophys Res Commun 290(5): 1593-1601
- Xie X, Ott J (1993) Testing linkage disequilibrium between a disease gene and marker loci. Am J Hum Genet 53: 1107
- Zhao JH, Curtis D, Sham PC (2000) Model-free analysis and permutation tests for allelic associations. Hum Hered 50(2): 133-139