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The Study On The Correlation And Clinical Value Between Main Markers Of RAAS And Angiotensinogen Gene Polymorphisms And Atrial Fibrillation

Posted on:2020-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:W Z ZhangFull Text:PDF
GTID:2404330575976488Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
Objective: To investigate the clinical diagnostic value of the main markers of renin-angiotensin-aldosterone system(RAAS)in atrial fibrillation;the correlation between the Single Nucleotide Polymorphism(SNP)of rs5046,rs2148582 of angiotensinogen-related genes(AGT)and the genetic susceptibility to atrial fibrillation and the RAAS expression,and to provide the clinical basis for the early diagnosis of atrial fibrillation.Methods: 100 cases of control group and 108 patients of atrial fibrillation who treated by catheter ablation were enrolled as the research subjects,there were 60 cases of paroxysmal atrial fibrillation,32 cases of persistent atrial fibrillation and 16 cases of permanent atrial fibrillation according to the duration of attack;36 cases of isolated atrial fibrillation,40 cases of hypertension with atrial fibrillation,32 cases of coronary heart disease with atrial fibrillation according to the basic diseases;the general clinical information of all subjects were collected,including sex,age,nationality,life habits,living habits,smoking history,drinking history,ultrasound finding,and the decubitus plasma levels of Ang?,PRA,ALD,cortisol were measured by chemiluminescence in preoperative and postoperative of atrial fibrillation and control group;the polymerase chain reaction(PCR)was used to amplify the the polymorphism of rs5046,rs2148582 of AGT gene,and the Pyrophosphate sequencing was used to detect polymorphisms of two loci,to analyze the genotypes distribution of gene;the association between rs5046 and rs2148582 polymorphism loci of AGT gene and the risk of atrial fibrillation was analyzed by the chi-square test,comparing the differences of polymorphism loci among with different clinical types and different underlying diseases in atrial fibrillation patients,and further stratified were analyzed by the general clinical factors which were grouped;One-way AVOVA was used to analyze the correlation between the genotypes of rs5046,rs2148582 loci and plasma Ang?levels;the risk factors of atrial fibrillation were analyzed by Logstic regression,using Pearson correlation coefficient(r)to describe the linear correlation of two continuous variables,the statistical software SPSS23.0 was applied to draw the ROC curve and the clinical value of the main markers of RAAS was evaluated the diagnosis of atrial fibrillation by the area under the ROC curve(AUC).Results:(1)There was significant difference in LAD between atrial fibrillation group and control group(P<0.05);compared with the preoperative,the plasma levels of Ang?,PRA,ALD and cortisol in the atrial fibrillation group of preoperative and postoperative were higher than those in control group(P<0.05);there was no significant difference in preoperative plasma PRA level between paroxysmal atrial fibrillation group and persistent atrial fibrillation group(P>0.05),and no significant difference was found in preoperative plasma ALD level and post-operative plasma PRA level between persistent atrial fibrillation group and permanent atrial fibrillation group(P>0.05)among different types of atrial fibrillation,but the differences in other groups was significant(P<0.05).(2)The genotype frequencies of CT and TT at rs5046 locus in atrial fibrillation group were significantly higher than those in control group(P<0.05);the genotype of TT had greater effect on atrial fibrillation than the genotype of CT(OR=4.38,95% CI: 1.35-14.19,P=0.009),and the difference in C and T allele frequencies between the two groups was significant(P<0.05),while no significant difference was observed in rs2148582(P>0.05);in the analysis of different clinical types subgroup of atrial fibrillation in rs5046 locus,there was no significant difference between the the permanent atrial fibrillation group and the control group in gene mutation(P>0.05),but the other two group were significant difference from the control group(P<0.05),no difference was noted in different basic diseases of atrial fibrillation in rs5046 locus(P>0.05);the results of hierarchical analysis showed that over 60-year-old individuals had an increased risk of atrial fibrillation[P=0.002;OR=2.397(95% CI:1.36~4.33)];and no significant differences was found in gender and ethnicity(P>0.05).(3)the results of the one-way ANOVA suggested that the levels of plasma Ang?in CC,CT and TT genotypes of rs5046 locus was was statistically difference(F=7.488,P=0.001),and the levels of plasma Ang?was gradually increased.(4)It was found that there was 8 possible risk factors in atrial fibrillation of Logistic regression analysis,and OR value and 95%CI indicated the degree of association between the two of them,six risk factors were screened out :LAD(OR=1.950),PRA(OR=4.993),Ang?(OR=1.163),ALD(OR=1.084),cortisol(OR= 1.026),rs5046 genotype(OR=2.758);the results of Pearson correlation analysis demonstrated that the AngII was associated with LAD(r=0.387,P=0.000),Ang?was associated with PRA(r=0.453,P=0.000),Ang?was associated with ALD(r=0.321,P=0.000),Ang?was associated with cortisol(r=0.459,P=0.000);ROC curve showed that the area under curve of Ang?was the largest among them,which was the 0.683.Conclusion:(1)Ang?,PRA and ALD of plasma levels,which are the main markers of RAAS,can be used as a index for the diagnosis of atrial fibrillation and the course assessment.(2)There was a correaltion between the polymorphism of rs5046 locus of AGT gene and the susceptibility to atrial fibrillation,and the allele T can increase the risk of atrial fibrillation.(3)The polymorphism of rs5046 is related to high plasma Ang?levels,which provides a reference for the screening and treatment of clinical atrial fibrillation.
Keywords/Search Tags:Atrial fibrillation, AGT, RAAS, Single neucleotide polymorphism
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