Increased 8-hydroxy-2'-deoxyguanosine in leukocyte DNA in Leber's hereditary optic neuropathy.
OBJECTIVE
This study was conducted to test the hypothesis that oxidative stress is involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON). The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized DNA base common in cells undergoing oxidative stress, was measured in leukocyte DNA from patients with LHON and normal control subjects.


METHODS
The 8-OHdG and deoxyguanosine (dG) content in leukocyte DNA from 25 patients with LHON with an 11778 mitochondrial (mt)DNA mutation, 14 asymptomatic maternal relatives, and 27 unrelated normal control subjects were measured using high-performance liquid chromatography and electrochemical detection methods.


RESULTS
The mean 8-OHdG/10(5) dG ratio from leukocyte DNA was 1.34 +/- 0.99 in patients with LHON, 1.00 +/- 0.91 in their asymptomatic maternal relatives, and 0.31 +/- 0.20 in normal control subjects, respectively. There was a statistically significant difference in the mean 8-OHdG/10(5) dG ratio between patients with LHON and normal control subjects and between asymptomatic maternal relatives and normal control subjects. The difference between patients with LHON and asymptomatic maternal relatives did not reach statistical significance.


CONCLUSIONS
Patients with LHON with an 11778 mtDNA mutation had higher oxidative DNA damage. Oxidative stress has a key role in the pathogenesis of LHON.
Yen
May-Yung
MY
Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan, Republic of China. myyen@vghtpe.gov.tw
Kao
Shu-Huei
SH
Wang
An-Guor
AG
Wei
Yau-Huei
YH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress
D015415:Biomarkers; D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine