| BackgroundIdiopathic premature ventricular contractions (IPVCs) is the most common clinical arrhythmia, is not associated with evidence of organic heart premature ventricular contractions. Past time It is look as a benign disease, but now found some of the IPVCs with organic heart changes, decreased heart function, easy to trigger a deadly serious ventricular tachycardia or ventricular fibrillation and sudden death. It was advocate for the clinical treatment of psychological comfort or anti-arrhythmic drugs symptomatic treatment, but the result is not satisfactory, the recurrence rate is high, resulting in patients with mental, emotional burden, reduce the quality of life. In recent years, with ablation technology, the most frequent idiopathic ventricular premature can cure, but its indication is controversial, only for frequent, symptoms and medication drugs ineffective IPVCs. Based on the problem of IPVCs, it is necessary to conduct in-depth study for pathogenesis. With the development of molecular genetics, molecular mechanisms of arrhythmias become clear and study the pathogenic gene polymorphism among populations has become possible, genetic characteristics is expected to guide the clinical prevention and treatment initiatives. Cardiac electrical activity is regulated by the autonomic nervous system,β1 adrenergic receptor is the majorβ-AR of heart and mediating the cardiac sympathetic-adrenal system of signal transduction.β1-AR gene has two important SNP:first polymorphic locus at nucleic acid 145(A→G)resulted in substitution of Ser for Gly at position49. second was observed at nucleic acid 1165(G→C)resulting in substitution of Gly for Arg at position 389.The codon 389 polymorphism is located in the proximal region of the carboxyterminus cytoplasmic tail, and the region is believed to be an important site for receptor coupling to the G-protein. In vitro mutagenesis studies of the codon 389 polymorphism revealed nearly twofold greater basal and threefold greater agonist-mediated adenylyl cyclase activities with the Arg389 receptor form Gly389, so we hypothesized that theβ1-AR genotype C389G locus may have functional significance In IPVCs. Research at abroad shows thatβ1-AR gene locus C389G SNP have relationship with the pathogenesis of IPVCs, and racial distribution of the gene is different, related research is not yet reported in Chinese. The aim of present study was to explore the relationship betweenβ1-AR gene C389G SNP and the occurrence or development of frequent IPVCs in Chinese by the technique of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).we hope to clarify the molecular genetics of IPVCs and provide a basis for prevention and treatment.Objective:144 patients with frequent idiopathic ventricular premature patients and 142 healthy controls in southern China Han population participated in this study. establishment of clinical data, Detect plasma renin activity (PRA) and heart rate turbulence (HRT) value TO and TS, Identify gene type ofβ1-AR gene C389G locus which maybe related to frequent idiopathic ventricular premature on the sympathetic nervous system and investigate the relationship between IPVCs, PRA, HRT andβ1-AR gene C389G SNP. Make out the possible pathogenesis role of the autonomic nervous in PVCs in South China Han population.Subjects:Subjects:All of the subjects were screened from inpatients and healthy in the southern hospital from 2007.09 to 2009.08. The inclusion criteria:①The number of PVCs≥720/24h on 24-hour Holter monitoring and be Analysis with HRT(with a PVCs that frontal 2 beats and afterwards 15 beats were Sinus rhythm).②Physical examination, chest radiography, echocardiography and other investigations failed to find structural heart disease.③No other important organs disorders, electrolyte disorders and other can induce factors. Exclusion criteria:①Non-sinus rhythm patients, such as atrial fibrillation, atrial flutter, temporary and permanent pacemaker implantation, etc.②patients with Sick sinus syndrome, atrioventricular block.③have taken antiarrhythmic drugs or any drugs affecting the autonomic nervous system. control group inclusion criteria:healthy volunteers:①The number of PVCs <100/24h on 24-hour Holter monitoring and meet the front inclusion criteria②③and the exclusion criteria. All subjects were in southern China Han population (unrelated), and have been informed consent.Based on above criteria, there were 144 patients enrolled in PVCs group, mean age 42.98±10.03,56 males and 88 females; 142 healthy cases in control group, mean age 42.01±8.96,51 males and 91 females.Methods:Both groups establish clinical data observation table and record name, sex, age, height, weight, blood pressure, smoking history, drinking history etc; Detect serum biochemical indicators:cholesterol (TC), triglyceride (TG), glucose, sodium, potassium, plasma renin activity (PRA); conducted 24 hours electrocardiogram examination:records the numbers of PVCs in 24h, heart rate, PVCs burden and conduct heart rate turbulence onset (TO), turbulence slope (TS). Reagents Box extraction research object venous leukocyte genome DNA, Identificationβ1-AR gene C389G polymorphism (SNP) with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Compare genotypes, allele frequency distribution and clinical datas between two groups. Compare TO, TS value and HRT abnormal rate in genotype. Compare PRA,TO,TS in different genotype after RFCA。Abnormal HRT defined:TO≥0% and (or) TS≤2.5ms/RR.Statistical analysis:SPSS13.0 statistical software was used. Measurement data which meet the normal distribution of mean±standard deviation, the count data of said frequency. Balance of genetic testing utilizes Hardy-Weinberg law of balance. To compare the groups of count data utilize testingχ2. Compared the groups of normal distribution measurement data by homogeneity of variance test, homogeneity of variance compared using by one-way ANOVA, multiple comparisons between groups using LSD method; two-sample comparison between the mean homogeneity from using an independent samples t test, variance from the use of irregular t'test. Single-variable logistic regression analysis to explore the relationship between gene polymorphism and atrial fibrillation occurred, calculated odds ratio (odds ratio, OR) and 95% confidence interval (95% CI). Standard test a=0.05.Results:1. There are 3 genotypes ofβ1-AR gene C389G SNP in Han population of southern China when identified by PCR-RFLP:1 denote CC genotype,2 denote CG genotype and 3 for the GG genotype. PVCs group and control group CC, CG, GG genotype rate were as follows:60.4%,33.3%,6.3% and 47.9%,38.7%,13.4%.2. Measurement data were normal distribution in two groups. age, sex, heart rate, weight index (BMI), smoking, drinking, SBP, DBP, Na, K, GLU, TG, TC were no significant difference between two groups, P values were 0.388,0.603,0.155, 0.510,0.942,0.598,0.143,0.168,0.331,0.608,0.956,0.739,0.932. PRA significantly different between two groups, P=0.000, PRA of PVCs group more than control group. TO, TS and HRT abnormal rate significant different between two groups, P values were 0.000,0.000 and 0.019, TO value of PVCs group more than control group, TS value less than control group, HRT abnormal rate higher in PVCs group.3. The genotype frequency ofβ1-AR gene C389G locus CC, CG and GG between two groups was significant different (χ2= 6.363, P=0.042).β1-AR gene C389G locus frequency of CC genotype was higher in PVCs group.β1-AR gene C389G allele genotype frequency was significant different between two groups (χ2= 6.884, P=0.009). C allele genotype frequency was higher in PVCs group.4. Univariate logistic regression analysis the relationship betweenβ1-AR gene C389G SNP with PVCs, in terms of relative CC genotypes, CG+GG genotype and homozygous GG genotype, a significant increase the risk of PVCs, OR value (95% CI) were 0.602 (0.377-0.962),0.370 (0.158-0.870), P values were 0.034,0.023, suggested that CG+GG genotype and the GG genotype was a protective factor PVCs. CG genotype OR values (95% CI) was 0.682 (0.414-1.125), P=0.134. The relative risk ofβ1-AR gene locus C389G G allele gene in PVCs, in terms of relative C allele, OR value (95% CI) was 0.611 (0.422-0.884), P=0.009.5. PRA values of three genotypes ANOVA F=7.374, P=0.001, all three genotypes had significant differences in PRA; LSD-t test was used to compare between two genotypes, PRA was significantly different between GG and CC, CG genotype, P values were 0.000 and 0.010, no significant difference between CC and CG genotype, P=0.088, PRA of CC and CG genotype was significantly higher than GG genotype.6. The variance F value of three genotypes in TO and TS analysis is 8.968 and 12.113, Both P value is 0.000. TO and TS values were significantly different in three genotypes. LSD-t test was used to compare between two genotypes, TO and TS values was significantly different between GG and CC, CG genotype, P values were 0.000,0.003 and 0.000,0.000. No significant difference between CC and CG genotype of TO and TS, P values were 0.085 and 0.055. TO in CC and CG genotype were significantly higher than GG genotype, TS in CC and CG genotype were significantly lower than GG genotype. The HRT abnormal rate in three genotypes was compare usingχ2 test,χ2=6.584, P=0.037, the abnormal rate of HRT in CC, CG and GG genotype were 30.3%,20.4% and 10.7%, the rate in CC and CG genotype were significantly higher than GG genotype.7. PRA, HRT indicators improved after Radiofrequency ablation of frequent IPVCs, compared of PRA,TO,TS with covariance analysis in different genotypes, F values were 3.595,3.663,3.355, P values were 0.033,0.031,0.041, PRA, TO, TS values were significantly different after RFCA. Comparison the PRA and HRT value of the adjusted mean shows:improvement of CC type is the maximum, CG type next, while the GG type is the minimum.Conclusion:1.β1-AR gene C389G SNP exists in the South China Han population, the genotype distribution frequency was difference between IPVCs group and control group.2. There is a clear correlation betweenβ1-AR gene C389G SNP and the incidence of IPVCs in Southern China Han population, G alleles are IPVCs occurred in the protection of genetic, C allele are IPVCs susceptibility gene.3. There is a clear correlation betweenβ1-AR gene C389G SNP and the HRT abnormal rate:GG |
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