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Background  The mitochondrial (mt) displacement loop (D-loop) is known to accumulate structural alterations and mutations. The aim of this study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) within the D-loop among chronic dialysis patients and healthy controls.    Methodology and Principal Findings  We enrolled 193 chronic dialysis patients and 704 healthy controls. SNPs were identified by large scale D-loop sequencing and bioinformatic analysis. Chronic dialysis patients had lower body mass index, blood thiols, and cholesterol levels than controls. A total of 77 SNPs matched with the positions in reference of the Revised Cambridge Reference Sequence (CRS) were found in the study population. Chronic dialysis patients had a significantly higher incidence of 9 SNPs compared to controls. These include SNP5 (16108Y), SNP17 (16172Y), SNP21 (16223Y), SNP34 (16274R), SNP35 (16278Y), SNP55 (16463R), SNP56 (16519Y), SNP64 (185R), and SNP65 (189R) in D-loop of CRS. Among these SNPs with genotypes, SNP55-G, SNP56-C, and SNP64-A were 4.78, 1.47, and 5.15 times more frequent in dialysis patients compared to controls ( P <0.05), respectively. When adjusting the covariates of demographics and comorbidities, SNP64-A was 5.13 times more frequent in dialysis patients compared to controls ( P <0.01). Furthermore, SNP64-A was found to be 35.80, 3.48, 4.69, 5,55, and 4.67 times higher in female patients and in patients without diabetes, coronary artery disease, smoking, and hypertension in an independent significance manner ( P <0.05), respectively. In patients older than 50 years or with hypertension, SNP34-A and SNP17-C were found to be 7.97 and 3.71 times more frequent ( P <0.05) compared to patients younger than 50 years or those without hypertension, respectively.    Conclusions and Significance  The results of large-scale sequencing suggest that specific SNPs in the mtDNA D-loop are significantly associated with chronic dialysis. These SNPs can be considered as potential predictors for chronic dialysis.

Sequence-Based Polymorphisms in the Mitochondrial D-Loop and Potential SNP Predictors for Chronic Dialysis