Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases
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.
fDepartment of Neurology, National Yang-Ming University, Taipei 112, Taiwan
gNeurological Institute, Taipei Veterans General Hospital, Taipei 112, Taiwan
hDepartment 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.
ABSTRACT