title: Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease.
abstract: BACKGROUND
  The mitochondrial displacement loop (D-loop) accumulates mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). We previously identified disease risk-associated SNPs in the D-loop of chronic kidney disease (CKD) patients; in this study, we investigated the association of age-at-onset and D-loop SNPs in CKD patients.
  
  
  METHODS
  The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. The age-at-onset curve of the CKD patients was calculated using the Kaplan-Meier method at each SNP site, and compared using the log-rank test.
  
  
  RESULTS
  The mean age of 119 CKD patients was (55.6±14.2) years, and 56.3% were males. The mean estimated glomerular filtration rate (eGFR) was (81.2±12.4) ml×min(-1)×1.73 m(-2), with 79.8% (n = 95) of patients having an eGFR <60 ml×min(-1)×1.73 m(-2). All participants had an eGFR >30 ml×min(-1)×1.73 m(-2). The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients. The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site (P = 0.010).
  
  
  CONCLUSIONS
  Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Departments of Gastroenterology and Hepatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China. Email: xjs5766@126.com.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Huiran
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Shenglei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Ai
mesh_terms: D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051436:Renal Insufficiency, Chronic / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial