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

Abstract

BackgroundThe 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 FindingsWe 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 SignificanceThe 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.

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

“…Consistent with earlier reports, our data demonstrated smoking and gender were associated with the CKD progression, [29][30][31][32][33] which confirmed the validity of our data. The mechanism explained the relationship between smoking and CKD progression is that smoking contribute to oxidative stress, which plays important role in the development and progression of CKD.…”

Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

“…Chronic inflammation is a common contributor to progressive renal failure and leads to premature mitochondrial DNA (mtDNA) damage. Pathogenic mutations in mtDNA represent an increasingly recognized cause of chronic morbidity, and mitochondrial mutations have been implicated in a range of complex disorders, including kidney disease [4][5][6]. There is a synergistic relationship between the mitochondrial and nuclear genomes, with the expression of nuclear genes being essential for critical mitochondrial functions.…”

Genetic Algorithm Combined with a Local Search Method for Identifying Susceptibility Genes

“…Thus, improved understanding of associations between SNPs contributes to the analysis of diseases and cancers [3][4][5]. Genetic associations indicate that the effect of any single genetic variation (e.g., SNPs) will likely be dependent on other genetic variations (interaction between SNPs) [6].…”