Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases

Liu, Chin-San; Cheng, Wen-Ling; Kuo, Shou-Jen; Li, Jie-Yuan; Soong, Bing-Wen; Wei, Yau-Huei

doi:10.1016/j.jns.2007.07.016

« Previous Next »Journal of the Neurological Sciences
Volume 264, Issue 1 , Pages 18-21, 15 January 2008

Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases

Chin-San Liu
- Department of Neurology and Vascular and Genomic Center, Changhua Christian Hospital, Changhua 500, Taiwan
- Graduate Institute of Integrative Chinese and Western Medicine, China Medical University Hospital, Taichung 404, Taiwan
- Corresponding authors. Liu is to be contacted at Department of Neurology & Vascular and Genomics Center, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua 500, Taiwan. Tel.: +886 4 7238595x4752; fax: +886 4 7238595x4063. Wei, Tel.: +886 2 28267118; fax: +886 2 28264843.
Wen-Ling Cheng
- Department of Neurology and Vascular and Genomic Center, Changhua Christian Hospital, Changhua 500, Taiwan
Shou-Jen Kuo
- Department of Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
Jie-Yuan Li
- Division of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei 112, Taiwan
Bing-Wen Soong
- Department of Neurology, National Yang-Ming University, Taipei 112, Taiwan
- Neurological Institute, Taipei Veterans General Hospital, Taipei 112, Taiwan
Yau-Huei Wei
- Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei 112, Taiwan
- Corresponding authors. Liu is to be contacted at Department of Neurology & Vascular and Genomics Center, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua 500, Taiwan. Tel.: +886 4 7238595x4752; fax: +886 4 7238595x4063. Wei, Tel.: +886 2 28267118; fax: +886 2 28264843.

Received 3 May 2007; received in revised form 4 July 2007; accepted 9 July 2007.

Abstract

Polyglutamine (poly-Q) diseases are late-onset neurodegenerative disorders arising from the expansion of an unstable CAG repeat in the affected gene, which is translated to a tract of glutamine residues. This kind of mutant proteins may be aggregated and accumulated, and thereby enhance cellular oxidative stress. In one of our previous studies (Free Radic. Res. 2003;37:1307-17), we found that alteration in the leukocyte mtDNA content is very sensitive to the level of oxidative stress in blood. Thus, we proposed that leukocyte mtDNA content may be used as a biomarker to predict the severity of clinical manifestation of poly-Q diseases. We recruited 50 healthy subjects and 114 patients with poly-Q diseases, including spinal cerebellar atrophy 2/3, spinal bulbar muscular atrophy, and Huntington chorea. We found that mtDNA in leukocytes was depleted in patients with poly-Q diseases (P<0.05). Moreover, the results showed that patients with lower mtDNA content more frequently manifested multiple-symptom disorders and had high CAG repeat numbers in the mutant genes. In conclusion, we suggest that leukocyte mtDNA content correlates with the length of GAG repeat and may serve as an index of the severity of poly-Q diseases.