Number of CAG repeats in POLG1 and its association with Parkinson disease in the Norwegian population

被引：23

作者：

Balafkan, Novin ^{[2
]}

Tzoulis, Charalampos ^{[1
,2
]}

Muller, Bernd ^{[1
,2
]}

Haugarvoll, Kristoffer ^{[1
,2
]}

Tysnes, Ole-Bjorn ^{[1
,2
]}

Larsen, Jan Petter ^{[2
,3
]}

Bindoff, Laurence A. ^{[1
,2
]}

机构：

[1] Haukeland Hosp, Dept Neurol, N-5021 Bergen, Norway

[2] Univ Bergen, Dept Clin Med, Bergen, Norway

[3] Norwegian Ctr Movement Disorders, Stavanger, Norway

来源：

MITOCHONDRION | 2012年 / 12卷 / 06期

关键词：

Parkinsonism; Polyglutamine; Neurodegeneration; Mitochondria; DNA-POLYMERASE-GAMMA; RECESSIVE ATAXIA; MUTATIONS; VARIANTS; DELETIONS; NIGRA;

D O I：

10.1016/j.mito.2012.08.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The number of CAG repeats in the mitochondrial DNA-polymerase gamma (POLG1) gene has been associated with Parkinson disease (PD) in some populations. We sequenced the CAG tract of POLG1 in 191 Norwegian patients with PD and an equal number of controls and found an association between non-10 or 11 CAG repeats and PD in our population. While our results were significant, this trend was not maintained following correction for multiple testing. We also performed a meta-analysis of all published studies including our own that shows PD is associated with the number of CAG repeats in POLG1. The meta-analysis reveals that the rare allelic variation encompassed by non-10 CAG repeats associates significantly with PD (p = 0.0017). Whether this reflects a direct influence of POLG on the pathogenesis of PD or linkage disequilibrium between POLG1 alleles and nearby, disease-influencing genetic variants remains unknown. (C) 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

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收藏

页码：640 / 643

页数：4

相关论文

共 28 条

[1] Incidence of Parkinson's disease in Norway: the Norwegian ParkWest study [J].

Alves, G. ;

Mueller, B. ;

Herlofson, K. ;

HogenEsch, I. ;

Telstad, W. ;

Aarsland, D. ;

Tysnes, O-B ;

Larsen, J. P. .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2009, 80 (08) :851-857

[2] Variations of the CAG trinucleotide repeat in DNA polymerase gamma (POLG1) is associated with Parkinson's disease in Sweden [J].

Anvret, Anna ;

Westerlund, Marie ;

Sydow, Olof ;

Willows, Thomas ;

Lind, Charlotta ;

Galter, Dagmar ;

Belin, Andrea Carmine .

NEUROSCIENCE LETTERS, 2010, 485 (02) :117-120

[3] RESPIRATORY-CHAIN ABNORMALITIES IN SKELETAL-MUSCLE FROM PATIENTS WITH PARKINSONS-DISEASE [J].

BINDOFF, LA ;

BIRCHMACHIN, MA ;

CARTLIDGE, NEF ;

PARKER, WD ;

TURNBULL, DM .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 1991, 104 (02) :203-208

[4] Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism [J].

Bonifati, V ;

Rizzu, P ;

van Baren, MJ ;

Schaap, O ;

Breedveld, GJ ;

Krieger, E ;

Dekker, MCJ ;

Squitieri, F ;

Ibanez, P ;

Joosse, M ;

van Dongen, JW ;

Vanacore, N ;

van Swieten, JC ;

Brice, A ;

Meco, G ;

van Duijn, CM ;

Oostra, BA ;

Heutink, P .

SCIENCE, 2003, 299 (5604) :256-259

[5] POLG1 polyglutamine tract variants associated with Parkinson's disease [J].

Eerola, Johanna ;

Luoma, Petri T. ;

Peuralinna, Terhi ;

Scholz, Sonja ;

Paisan-Ruiz, Coro ;

Suomalainen, Anu ;

Singleton, Andrew B. ;

Tienari, Pentti J. .

NEUROSCIENCE LETTERS, 2010, 477 (01) :1-5

[6] Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-γA [J].

Ferrari, G ;

Lamantea, E ;

Donati, A ;

Filosto, M ;

Briem, E ;

Carrara, F ;

Parini, R ;

Simonati, A ;

Santer, R ;

Zeviani, M .

BRAIN, 2005, 128 :723-731

[7] Diagnostic criteria for Parkinson disease [J].

Gelb, DJ ;

Oliver, E ;

Gilman, S .

ARCHIVES OF NEUROLOGY, 1999, 56 (01) :33-39

[8] Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders [J].

Gu, GY ;

Reyes, PF ;

Golden, GT ;

Woltjer, RL ;

Hulette, C ;

Montine, TJ ;

Zhang, J .

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2002, 61 (07) :634-639

[9] Mitochondrial DNA polymerase W748S mutation:: A common cause of autosomal recessive ataxia with ancient European origin [J].

Hakonen, AH ;

Heiskanen, S ;

Juvonen, V ;

Lappalainen, I ;

Luoma, PT ;

Rantamäki, M ;

Van Goethem, G ;

Löfgren, A ;

Hackman, P ;

Paetau, A ;

Kaakkola, S ;

Majamaa, K ;

Varilo, T ;

Udd, B ;

Kääiäinen, H ;

Bindoff, LA ;

Suomalainen, A .

AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 77 (03) :430-441

[10] Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion [J].

Hakonen, Anna H. ;

Goffart, Steffi ;

Marjavaara, Sanna ;

Paetau, Anders ;

Cooper, Helen ;

Mattila, Kimmo ;

Lampinen, Milla ;

Sajantila, Antti ;

Lonnqvist, Tuula ;

Spelbrink, Johannes N. ;

Suomalainen, Anu .

HUMAN MOLECULAR GENETICS, 2008, 17 (23) :3822-3835