| Background and objectives: Nowadays, acute coronary syndrome(ACS) are the leading cause of mortality among ischemia heart disease(IHD). An early diagnosis is of absolute necessity for appropriate therapeutic decision and risk stratification in patients with ACS. Mitochondria play essential roles in several fundamental cellular processes, most notably energy metabolism, redox state and apoptosis, moreover produce of reactive oxygen species(ROS) associated with this organelles closely. Unlike nuclear DNA, mitochondrial DNA(mt DNA) is less protected by histones and appears to have less efficient repair mechanisms, which makes mt DNA particularly vulnerable to ROS and other genotoxic damage. It has been reported recently that mt DNA lesion was related to genesis and development of atherosclerosis and IHD, and mt DNA content have recently emerged as a factor associated with the initiation and development of cardiovascular disease(CVD), however, association between them and ACS was rarely covered in previous study, and its significance remains unclear. In this study, we aim to explore whether mt DNA content in peripheral blood leukocytes(PBLs) could be used as a risk predictor for ACS and its potential correlation with Gensini score.Methods: This cross-sectional study was consisted of 400 individual age from 31-87 years old who suspected with ACS. All the study population were consecutively recruited from the Xijing hospital. Genomic DNA was extracted from PBLs of all samples using the Qiagen blood DNA Midi Kit. A quantitative real-time PCR was conducted to measure the relative content of mt DNA in PBLs. At the time of sampling, epidemiological information of each subject was collected using a standardized questionnaire by well-trained staff interviewers, including age, gender, smoking habits, hypertension history and diabetes mellitus(DM). Detailed clinical data were abstracted from physical measurement or biochemical assay by treating physicians, including body mass index(BMI), white blood cell(WBC), triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), uric acid(UA), creatinine(Cr) and fasting glucose. Gensini score was used to evaluate the severity of coronary stenotic lesions. Subjects were dichotomized into four groups according to the quartile of the Gensini score. All statistical analyses were performed using the SPSS Statistics 22.0 software(IBM) and Graph Pad Prism 6.02 software. Pearson χ2 test was used to examine correlation between gensini score and mt DNA content. Student’s t test was used to test differences in normally distributed continuous variables(TC, TG, HDL-C, LDL-C, BMI, UA, Cr and glucose), and Manne Whitney U test for abnormally distributed continuous variables(mt DNA content) among four groups. The mt DNA content was also analyzed as a categorical variable by grouping it based on the median, quartile values in the controls. Logistic regression models were developed to estimate the association between ACS risk and mt DNA content by using odds ratio(OR) and 95% confidential interval(95% CI). All P values reported were two-sided, and P< 0.05 was considered to be statistically significant. This study is registered with Clinical Trials.gov, number NCT02500823.Results: 1. Four group on basis of the quartile of the Gensini score were well-matched on separate index in baseline characteristics, such as sex(P=0.163), age(P=0.812), BMI(P=0.623), DM history(P=0.110), hypertension history(P=0.072) and smoking habits(P=0.363). 2. ACS patients, compared to those without ACS, had lower mt DNA content [median, 0.78(0.61-1.02) vs. 0.83(0.70-1.15), P<0.001], and the mt DNA levels significantly decreased following an increasing Gensini score [0-22 group, 0.84(0.70-1.15); 22-55 group, 0.81(0.70-1.01); 55-96 group 0.79(0.70-0.98) and more than 96 group 0.77(0.61-0.94), P<0.001]. 3. Spearman correlation analyses indicated the Gensini score was negatively associated with mt DNA contents(r=-0.387, P<0.001). 4. We performed an unconditional logistic regression analysis to assess the association between mt DNA content and ACS risk. When individuals were classified into high and low groups based on the median value of mt DNA content in controls, we observed that low mt DNA content was significantly associated with a 2.34-fold(95% CI, 1.43-3.83, P<0.001) increase in risk of ACS after adjustment. By using the subjects in the first(highest mt DNA content) quartile as reference, the adjusted ORs(95% CIs) for individuals in the second, third and highest quartile of mt DNA content were 1.78(95% CI, 1.15-3.51), 2.21(95% CI, 1.65-3.74) and 4.83(95% CI, 2.67-8.64), respectively.Conclusions: These preliminary results suggest that mt DNA contents are significantly correlated with individual’s susceptibility to developing ACS and it can be regarded as an independent risk factor for ACS. |
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