Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan.
BACKGROUND
Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA.


RESULTS
Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% vs. 31.5%), 8-C (35.3% vs. 43.2%), and 9-10C (24.5% vs. 22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences.


CONCLUSIONS
Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.
Chen
Jin-Bor
JB
Nephrology Division, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan. jbchen1@ms5.hinet.net
Lin
Tsu-Kung
TK
Liao
Shang-Chih
SC
Lee
Wen-Chin
WC
Lee
Lung-Chih
LC
Liou
Chia-Wei
CW
Wang
Pei-Wen
PW
Tiao
Mao-Meng
MM
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D006435:Renal Dialysis; D012091:Repetitive Sequences, Nucleic Acid; D013624:Taiwan
D017931:DNA Primers; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species