title: Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan.
abstract: 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.
authors.affiliation: Nephrology Division, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan. jbchen1@ms5.hinet.net
authors.forename: Jin-Bor
authors.initials: JB
authors.lastname: Chen
authors.forename: Tsu-Kung
authors.initials: TK
authors.lastname: Lin
authors.forename: Shang-Chih
authors.initials: SC
authors.lastname: Liao
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Lee
authors.forename: Lung-Chih
authors.initials: LC
authors.lastname: Lee
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Liou
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Wang
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
mesh_terms: 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
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species