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

被引：26

作者：

Anvret, Anna ^{[1
]}

Westerlund, Marie ^{[1
]}

Sydow, Olof ^{[2
]}

Willows, Thomas ^{[2
]}

Lind, Charlotta ^{[2
]}

Galter, Dagmar ^{[1
]}

Belin, Andrea Carmine ^{[1
]}

机构：

[1] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden

[2] Karolinska Univ Hosp, Dept Clin Neurosci, Neurol Sect, S-17176 Stockholm, Sweden

来源：

NEUROSCIENCE LETTERS | 2010年 / 485卷 / 02期

基金：

瑞典研究理事会;

关键词：

Neurodegeneration; Dopamine; Mitochondria; mRNA; Poly-Q; NEURODEGENERATIVE DISORDERS; MITOCHONDRIAL DYSFUNCTION; HUNTINGTONS-DISEASE; W748S MUTATION; GENE; PATHOGENESIS; PREDICTION; VARIANTS; ATAXIA;

D O I：

10.1016/j.neulet.2010.08.082

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

DNA polymerase gamma (POLG1) is coding for the catalytic subunit of the heterotrimeric mitochondrial DNA polymerase and involved in replication and repair of mitochondrial DNA. In addition to its 5' to 3' polymerase activity. POLG1 has a 3' to 5' exonuclease activity important in the repair process Mitochondrial dysfunction has been implicated in neurodegenerative disorders like Parkinson's disease (PD). Dopamine neurons, which degenerate in PD, are believed to be particularly susceptible to mitochondrial dysfunction, which makes POLG1 a possible candidate gene for the disease. POLG1 has a polyglutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2. Most commonly the poly-Q tract comprises 10 repeats (10Q, frequency >80%) or moderately common 11Q (frequency 6-12%), however the composition of poly-Q alleles has been reported to vary from 6Q to 14Q We analyzed this POLG1 trinucleotide repeat in a Swedish PD case-control material and detected variations from 5Q to 15Q. We report a significant association between the non-10/11Q repeats with PD (p=0.002). In silica analysis of poly-Q length effect on mRNA folding energy show a decrease in energy for <10/11Q mRNA (4.6%) and an increase for >10/11Q mRNA (4.8%) compared to 10/11Q mRNA. Our results strengthen the evidence for involvement of POLG1 and mitochondrial dysfunction in PD (C) 2010 Elsevier Ireland Ltd. All rights reserved

引用

页码：117 / 120

页数：4

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