Analysis Of The Inducement And Prodrome Of Vasovagal Syncope And Research Of T393C SNP In The GNAS1 Gene

Background:Vasovagal syncope is a kind of neurally mediated reflex,which induced by nervous reflection and displayed hypotension or bradycardia.It is characterized by hypopiesia,bradycardia or appearance of autonomic nerve excitation such as pallor,nausa,sweating,hyperventilate,and so on.The diagnosis of vasovagal syncope is based on case history and confirmed by the head-up tilt table test.The vasovagal syncope is divided into three types according to the head-up tilt table test of character of hemodynamics:typel mixed,type2:cardioinhibitory,type3:pure vasodep- resssor.Although it rarely threatening life,vasovagal syncope may affect quality of life such as frequent seizures occur in some patients and even lead to serious accidents,such as falls,head trauma especially in the elderly.It is circumscribed for tilt table test to diagnosis vasovagal syncope because of the sensitivity of 26-80%and the specificity of 90%.Detailed case history of unexplained syncope patients is significant and is helpful to diagnosis and understand the charact eristic of the pathogenesis.Therefore,we study the characteristics of the inducement and prodrome of vasovagal syncope and aim to Provide more effective diagnosis means for vasovagal syncope.The pathophysiology of reflex responsible for classical vasovagal syncopy is not completely understood.Up to now,no certain genetic background of vasovagal syncopy has been reported.The heterotrimeric G protein,which responsible for the signal transduction from the cell surface,play a very important role in cardiovascular system.They are acticated by 7 transduction-helix receptors,G-protein coupled receptors(GPCR),eg,the adrenergic receptors.G protein is composed of 3 subunits designated asα,β,andγ.Each subunit is encoded by a different gene.In the cardiovascular system,the a subunit of Gs(s-stmulated) protein(GNAS1) couples theβ-adrenergic receptors to the stimulation of cyclic adenosine monophophate(cAMP) production.A silent single nucleotide transition T/C within codone 131(ATT→ATC,IIe) in exon 5 of gene encoding GNAS1(GeneID:2778),loacated on chromosome 20q(20q13.2) locus 393,leads to enhanced activity of adenylyl cyclase.This disorder might be one of the important determinants causing syncope in reflex-mediated mechanism.Thus,the aims of the study were the evaluation to GNAS1 T393C polymorphism manifestation in syncopal patients and the analysis of the connection between the head-up tilt test(HUUT) results and alleles frequencies.Objectives:To study the characteristics of the inducement and prodrome of vasovagal syncope and evaluate the predicting value in patients who related clinical characteristics and estimate GNAS1 T393C polymorphism manifestation in vasovagal patients.Methods:167 unexplained syncope patients were made basis tilt test and nitroglycerin provocation test.A multifunctional monitor was used for the measurement of changes of blood pressure and electrocardiogram automatically.According to VASIS(vas-ovagal syncope internationgal study),the tilt test positive type are as follows:type1 mixed,type2A cardioinhibitory without asystole,type2B cardioinhibitory with asystole,type3,vasodepressor.Exceptions to this classification,include chronotropic incompetence,excessive heart rate rise(heart rate＞130bpm).Inducement and prodrome of 167 syncope patients were analysed and compared with the results of heat-up tilt testing on the correlation,predicting the results of HUUT.In 120 positive tilted patients(A group ) and 47 negative patients(B group),the genomic DNA was extracted from blood and the GNAS1 T393C polymorphism was diagnosed by restriction of the PCR amplicon with FokI(MBI).All patients were genotyped for GNAS1 and next analyzed regarding their head-up tilt table test results:.We have compared the distribution features of CC,CT,TT allele between the two groups.the statistical analysis of results:All data are presented as mean value±standard of the mean.Allele and genotype frequencies were obtained by direct counting.The significance of differences between groups was assessed using Chi-square test. Qualitative data expressed as a percentage were compared by Chi-square test,with Yates correction.Logistic regression was used for multivariate analysis.Statistically significant difference was defined as P＜0.05.All analyses were performed using the SPSS 13.0 statistical software.Results:All patients were able to tolerate tilt testing.One hundred and twanty (71.8%) patients had a positive result.The most common type of response was mixed type(60.0%) followed by vasodepressor(25.8%) and cardioinhibitory(14.2%) types. There were no significant differences in age groups,blood pressure,heart rate and number of syncope in positive(+HUUT) vs negative(-HUUT) tilting.67.1%and 93.4 %of patients with unexplained syncope had inducement and prodrome.Familiar inducements were prolonged standing(42.9%),change of position(21.4%),hot or warm environments(15.2%);Ten common prodromes about the vasovagal syncope had been summarized.They were dizziness(76.6%),pale(26.9%),hypodynamia(52.6%), nausea or vomiting(44.9%),sweating(46.1%),paraesthesia(14.9%),palpitation(25.1%), amaurosis(22.8%),chest istress(5.9%),amblyacousia(27.5%).Among patients with a positive response,the dizziness(OR:54.015 CI=13.992～208.520,P=0.000), hypodynamia(OR:4.762,CI=1.597～114.199,P=0.005),vomiting(OR:4.550,CI= 1.226～16.881,P=0.024),sweating(OR:8.897,CI=2.592～31.163,P=0.001) could predicted the positive result of HUTT.The prevalence of genotype CC,CT,TT was 21.7%,53.3%,25.0%respectively in positive tilted patients.And it was 6.4%,42.5%,51.0%in negative tilted patients respectively.In positive tilted patients,the GNAS1 T393C polymorphism had significant influence on blood pressure(P=0.015,P=0.006).The FokI+ allele frequency was higher in positive tilted patients compared with those with negative tilting results(48.3%vs 27.7%,χ~2=11.81 P=0.001).When comparing positive HUTT with cardioinhibition,vasodepressore component results and negative HUTT,the frequencies of the FokI+ were dereased among these groups:55.8%,47.1%,27.7%,respectively.The presence of C allele of GNAS1 gene was found to be a greater risk factor in positive tilted patients than in negative tilted patients.The odds ratio(OR95%CI) of CC,CC+TC and TC were 6.933 (1.871～25.699),3.130(1.546～6.339),2.560(1.228～5.339).And the P were 0.004,0.002,0.012,respectively。Conclusion:Vasovagal syncpe patients occupy a substantial proportion of unexplained syncope patients.The majority of them is mixed vasovagal response, followed by cardioinhabitory response and vasodepressor response.The result of HUTT could be predicted by some significant symptoms such as dizziness,collapse,sicchasia and diaporesis,which could be learned by inquiring about the case history of syncope patients.The GNAS1 T393C polymorphism is concerned with the results of vaso- vagal syncpe.The predisposition to vasovagal syncope seems to be associated with the GNAS1 FokI+ allele.