Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients.

BACKGROUND: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and SNPs at a higher frequency than other regions of mitochondrial DNA (mtDNA). We had identified chronic kidney disease (CKD) risk-associated SNPs in the D-loop of CKD patients previously. In this study, we investigated the association of SNPs in the D-loop of mtDNA with the kidney survival of CKD. METHODS: The D-loop region of mtDNA was sequenced for 119 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University. The Kaplan-Meier method was used to identify disease outcome-associated SNPs in the D-loop of CKD patients. The Cox proportional hazards model was used to identify risk factors for the kidney survival of CKD. RESULTS: In the present study, we identified 20 SNPs with a frequency higher than 5% and assessed the relationship of these SNPs with kidney survival time in CKD patients, a SNP of 146 was identified by log-rank test for statistically significant prediction of the kidney survival time. In an overall multivariate analysis, allele 146 was identified as an independent predictor of kidney survival time in CKD patients. The survival time of kidney in the CKD patients with 146C was significantly shorter than that of kidney in CKD patients with 146T (relative risk, 2.336; 95% CI, 1.319-3.923; p = 0.001). CONCLUSION: SNPs in the D-loop can predict the kidney survival of CKD patients. Analysis of genetic polymorphisms in the mitochondrial D-loop can help to identify CKD patient subgroup at high risk of a poor disease outcome.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease.

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.

Association of sequence polymorphism in the mitochondrial D-loop with chronic kidney disease.

BACKGROUND: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). METHODS: This is a case-control study. We sequenced SNPs in the D-loop of mtDNA and investigated their association with the risk of chronic kidney disease (CKD). RESULTS: A total of 144 SNPs referring to the positions of the Revised Cambridge Reference Sequence (rCRS) for mitochondrial genome were identified in a case-control study. The minor alleles of nucleotides 73G, 146C, 150T, 194T, 195C and 310C were associated with an increased risk for CKD patients. CONCLUSION: Analysis of genetic polymorphisms in the mitochondrial D-loop can help identify the people who are at a high risk of developing chronic kidney disease. These SNPs can be considered as potential predictors for CKD.