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- Title
Single Nucleotide Polymorphisms in the D-Loop Region of Mitochondrial DNA and Disease-Risk and Outcome of Chronic Kidney Disease.
- Authors
Sheng-lei Zhang; Jin-sheng Xu; Jun-xia Zhang; Li-wen Cui; Hui-ran Zhang; Qi-yao Yu
- Abstract
Objective: To analysis the characteristic of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of the mitochondrial DNA (mtDNA) and investigate the association of disease-risk and outcome of Chronic kidney disease (CKD) with the SNPs in D-loop of the mtDNA, we aimed to seek the biomarker for the development and progression of CKD. Methods: The D-loop region of mtDNA was sequenced in 88 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. In the 88 CKD patients, 42 were male and 46 were female, with mean age 54.6 ± 17.1 years. Blood samples were also collected from age-matched healthy controls. Total DNA was extracted using a Wizard Genomic DNA extraction kit (Promega, Madison, WI, USA) and stored at -20°C. PCR was performed using a PCR Master Mix Kit according to the manufacturer's instructions (Promega, Madison, WI), and the PCR products were purified before sequencing. Cyclic Cycle sequencing was performed with the Dye Terminator Cycle Sequencing Ready Reaction Kit (Applied Biosystem, Foster City, CA, USA) and the products were then separated on the ABIPRISM Genetic Analyzer 3100 (Applied Biosystem). Polymorphisms were confirmed by repeated analyses from both strands. The χ² test was used to analyze dichotomous values, such as the presence or absence of an individual SNP in CKD patients and healthy controls. The kidney survival curve was calculated using the Kaplan-Meier method, and compared with the logrank test. Multivariate survival analysis was performed using a Cox proportional hazards model. All statistical analyses were performed using the SPSS13.0 software (SPSS Company, Chicago, IL, USA). For all the statistical tests, p < 0.05 was considered statistically significant. Results: The sex and age of CKD patients were no significantly differ from those of healthy control (P > 0.05). SNPs in reference to GenBank accession AC - 000021 were detected at 98 sites of the 982-bp mitochondria D-Loop region from the CKD patients and the healthy controls. The SNP frequency for the 73G, 146C, 150T, 195C and 16266C in the CKD patients were higher than those in the health controls, but the SNP frequency for the 16290T in CKD patients was lower than that in healthy controls. Smoking habit showed an association with survival rates of kidney in CKD patients when the survival time of kidney in smoking CKD patients was lower than those in nonsmoking CKD patients. The survival rates of kidney in higher body mass index (BMI) CKD patients was higher than those in lower BMI CKD patients. The survival time of kidney in the CKD patients with the rare allele 146C genotype was significantly shorter than that of CKD patients with the frequent allele 146T. These data demonstrated that smoking and SNP at 146 site were the risk factors for the kidney outcome of CKD patients in the multivariate analysis by the Cox proportional hazards model. Conclusions: SNPs in the mtDNA D-loop were found to be independent prognostic markers for the disease-risk and the kidney survival time in CKD patients. The analysis of genetic polymorphisms in the D-loop might help to identify CKD patient subgroups at high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.
- Subjects
SINGLE nucleotide polymorphisms; MITOCHONDRIAL DNA; CHRONIC kidney failure; GENETIC polymorphisms; PATIENTS; DISEASE risk factors
- Publication
Blood Purification, 2016, Vol 41, Issue 4, p296
- ISSN
0253-5068
- Publication type
Article
- DOI
10.1159/000443804