Clinic Research On Associations Between SIRT3 Gene Polymorphism And Chronic Heart Failure In Senior Population

Background:As our country develops into the aging society,the incidence of heart failure has gradually increased.Heart failure is a serious threat to health and severely affects the quality of human life,especially for the elderly.Chronic heart failure is an irreversible development process,with a complex regulatory mechanism.SIRT3 is a stable protein associated with longevity in mitochondria.SIRT3 enhances antioxidant defense and protects mitochondrial function by adjusting mitochondrial acetylation activity.Mitochondrial dysfunction plays the central role of many cardiovascular diseases such as hypertrophic and dilated cardiomyopathy,heart failure,early atherosclerotic endothelial dysfunction and pulmonary hypertension.Furthermore,SIRT3 protein can be affected by oxidative phosphorylation,tricarboxylic acid cycling and beta-Oxidation to regulate cell metabolism,suggesting that it is closely related to metabolic syndrome.Studies have found that SIRT3 gene single nucleotide polymorphisms increase the risk of individual metabolic syndrome.And the above process is also closely linked with heart failure.Therefore,this study focused on the effects of single nucleotide polymorphisms encoding SIRT3 on chronic heart failure in the elderly.Objectives:(1)To study the expression of SIRT3 gene polymorphism in elderly patients with chronic heart failure.(2)To study the relationship between SIRT3 gene polymorphism and different components of chronic heart failure in the elderly.(3)To explore the relationship between SIRT3 gene polymorphism and chronic heart failure in the elderly and its possible mechanism.Methods:1.SubjectsAccording to the CSC guidelines for the diagnosis and treatment of heart failure in China published in 2014,105 samples(52 females,mean age 67.15 ± 6.35 yrs)of hospitalized heart failure patients were chosen in the Second Hospital of Shandong University from July 2015 to July 2016.The exclusion criteria were pulmonary embolism,acute myocardial infarction,multiple organ failure syndrome and other diseases.We randomly selected 98 healthy volunteers as control subjects in Health Management Center of physical examination,including 51 males and 47 females,mean age were 67.36±5.93 yrs.The volunteers were performed the laboratory tests and a variety of auxiliary examination and were excluded various organic diseases.2.Detection of cardiac ultrasound and biochemical markers(1)Completed within 24 hours after admission,all subjects were measured with GE Vivid7 color Doppler ultrasound imaging device for inspection by the professional operation physician.(2)Blood sugar(BG),triglyceride(TG),total cholesterol(TC),very low density lipoprotein cholesterol(VLDL),high density lipoprotein cholesterol(HDL-c)were measured.3.Experimental methods(1)Fasting peripheral venous blood samples were collected from elderly patients with chronic heart failure and volunteers.The bloods were centrifuged and divided the serum,red blood cells and white blood cells into three layers after ultracentrifugation,and white blood cells were extracted.(2)The white blood cells were put in the sterile EP tube,DNA extraction were kept in the environment of minus 80 degrees tube frozen.(3)PCR and test the polymorphism of rs11246020 locus of SIRT3 gene.4.Statistical analysisSPSS22.0 analysis software was used to analyze the data obtained.The mean ±standard deviation(x±s)indicated the measurement data,and the Student't test was used to compare the samples.Then the allele frequency of each group was calculated by fitting goodness test,and the Hardy-Weinberg gene genetic test was used to judge the representation of the sample.The data logistic regression analysis was used to explore the relationship between rs11246020 polymorphism and chronic heart failure.If P<0.05,it is present that the difference was statistically significant.Results1.The distribution of AA,AG,GG genotype and its allele in the normal control group and the heart failure group were consistent with the Hardy-Weinberg genetic pattern,and the difference between the two groups was statistically significant(P<0.05).2.Compared with the control group,the levels of BNP,BS,TG,TC and VLDL were higher in the HF group(P<0.05).LVEF and HDL decreased in the HF group(P<0.05).3.The individuals with AG + AA alleles in elderly patients with chronic heart failure had high blood glucose levels(P<0.05)compared with individuals carrying GG alleles.Individuals carrying the AG + AA allele had higher cholesterol levels(P<0.05)than those carrying the GG allele.4.The individuals carrying the GG allele in elderly patients with chronic heart failure had lower BNP levels compared with individuals carrying the AG + AA allele.The individuals carrying the GG allele compared with individuals carrying the AG + AA allele had a higher ejection fraction,(P<0.05).5.Logistic regression analysis showed that AA + AG(P<0.001),blood glucose(P<0.001),triglyceride(P<0.05)and cholesterol(P<0.01)were able to enter the regression equation,There was a quantitative correlation between the BNP and the rs11246020 polymorphism A allele of the SIRT3 gene.Conclusion1.The rs11246020 polymorphism A allele in the SIRT3 gene is associated with chronic heart failure and may play an important role in the regulation of chronic heart failure.2.The polymorphism of SIRT3 gene may affect and participate in the development and progression of chronic heart failure in the elderly.However,the specific mechanism is not clear and needs to be studied further.