Preliminary Studies Of Prevalence And Prognosis About Brugada-type ECG In Healthy Examination And Research Of H558R SNP In The SCN5A Gene

BackgroundBrugada syndrome is a kind of congenital "ion channelopathy" first describedby Brugada in 1992. Inheritance of the Brugada syndrome is via an autosomaldominant mode of transmission. Brugada syndrome is. characterized bypolymorphous ventricular tachycardia(PVT), ventricular fibrillation(VT) and suddendeath,An essential condition for its diagnosis is Brugada-type electrocardiogram(ECG), which character is a typical ECG pattern that consists of varying degreesof right bundle branch block (RBBB) and ST-segment elevation in the V1-V3leads, coved or saddleback-shaped. The disease had draw world wide attention sinceit was frequently seen in young male adults (especially in Southeast Asian) and isassociated with high incidence rate of sudden death.Brugada syndrome is widely distributed in all over the world,There aremany overseas reports about the prevalence rate of Brugada-type ECG in Japaneseand in other asian conuntry, especially in Southeast Asian, because, we are near tothese country, and There are more and more reports about the case of Brugada syndrome in our country, Thus, maybe,our country enjoy the highest occurrencerate Of Brugada ECG. a preliminary study focusing on the prevalence of BrugadaECG pattern was performed by retrospectivly investigating 23,082 ECGs recordedfrom non-cardiac inpatients admitted to our clinic institute in recent years. There aremany Brugada syndrome patients which were reported in our previousstudy, also, there are lacked in the system Epidemiology of Brugada syndrome.The investigation could help us know the prevalence of the Brugada-type ECG andthe relations between the Brugada-type ECG and Brugada syndrome by collectinglarge quantity of ECGs. Further more, it will benefit screening of mutations ofSCN5A and preparation for gene diagnosis and treatment.The only gene known to be linked to Brugada syndrome is SCN5A, Singlenucleotide polymorphisms (SNPs), DNA sequence variations that are common inthe populations, have been implicated in phenotypic variability inphysiology, pharmacology, and pathophysiology, Studies have linked genepolymorphisms to elevate risks of cysticfibrosis, Alzheimers diseases, and even heartdiseaseRecently, the polymorphism in the SCN5A are found to increase the risk ofarrhythmia in general populations,There are 39 polymorphism in the SCN5A genewhich have been reported in oversea. And H558R SNP are contributed to therisk of arrhythmia, so,we study the characteristics of H558R SNP and distributions ofgenotype and allele frequencies of SCN5A SNPs, To investigate its association withBrugada-type ECG.Lone AF is the frequency complication of Brugada syndrome, there arenearly 30% Brugada syndrome patients associated with Lone AF. so,westudy the distributions of genotype and allele frequencies of SCN5A SNPs betweenLone AF group and the healthy group, to investigate H558R are linkd to Lone AF.Methods1,45152 ECGs recorded of the physical examination center in our hospital werecollected for analysis.The criterion of Brugada-type ECG was in accordance with themorphology defined in the Consensus Report: Type 1 is diagnostic of Brugadasyndrome and is characterized by a coved ST-segment elevation≥2mm followed by anegative T wave. Type 2 has a saddleback appearance with a high take-offST-segment elevation of≥2mm followed by a trough displaying≥1mm ST elevationfollowed by either a positive or a biphasic T-wave. Type 3 has either a saddleback oracoved appearance with an ST-segment elevation of＜1mm.2,The peoples with Brugada-type ectrocadiogram were divided into two groups(A) Patients are finally diganosised as Brugada syndrome (who had syncope ofunknown origin or had the family history of sudden death) (B) 73 were asymptomatic3,Genomic DNA was extracted from peripheral blood of all of the patients Thepeople were divided into three groups: (A) 200 were unrelated healthyvolunteers (B) 82 were diganosised as electrocardiographic sign of Brugadasyndrome (C) 102 Patients are finally diganosised as lone AF. after GenomicDNA was extracted, H558R SNPs in SCN5A gene were detected by PCR-SSCPand the genotypes of SNPS in SCNSA gene determined by restriction enzymeanalysis.4,Statistical methods: Data were generally expressed in the forms:(?)±S,Chi-square test was used to test the difference in prevalence rate. and P value＜0.05was considered statistically significanceRsults:1,Brugada ECG pattem was seen in 1.82‰(82 of 45152) of the patients, including 73 males and 9 females. Among them, 18 ECGs (0.40‰) were classifiedas Brugada ECG pattern typeⅠ, 38 (0.84‰) typeⅡand 26 (0.58‰) typeⅢ, Thereare difference in the occurrence rate Of Brugada-type ECG between themale and female. (X~2=19.989,P＜0.001) also,There are difference in theoccurrence rate Of Brugada ECG between the 30-39 group and the otherage groups. (P＜0.05), the 30-39 group of the occurrence rate is the highest inall groups.2,After a mean follow-up period of 24 (standard deviation,12) months, newfatally arrhythmic events occurred in 22% (2/9) of patients in group A and 2.8%(2/12) of patients in group B, respectively. Nobody was died of sudden death.3,The distribution of the H558R SNP in the 12 exon is following:HH is 80.5%(161cases), HRis 15.0%(30 cases),RRis 4.5% (9 cases),the H allele frequencies of H558R SNP is 88.0%, the R allele frequencies ofH558R is 12.0% 4,There are difference in the three geneotypes of H558R SNPbetween the Brugada ECG group and the healthy group. The occurrencerate Of HR and Ralleles in the Brugada ECG group is higher than inthe healthy group. 5,There are difference in the three geneotypes of H558R SNPbetween the lone AF group and the healthy group. The occurrence rateOf HR and R alleles in the lone AF group is higher than in the healthygroupConclusions1,The Brugada-type ECG is not infrequent in Chinese. the occurrence rateOf Brugada-type ECG is 1.82‰, the gender ratio of male to female is 4:1, The30-39 group of the occurrence rate is the highest in all group. 2,Chinese patients with Brugada syndrome have a high likelihood ofarrhythrnia recurrence, aggressive measure must be taken for the prevent and treatarrhythmia, whereas asymptomatic patients enjoy a good short-term prognosis.3,The H558R in the 12 exon in SCN5A gene coding exist in Hanpopulation of China.4,There is a close connection between the H558R SNP and the Brugada-typeECG in Han population and the R allele probably may be pathogenic H alleleMay be protective for Brugada-type ECG..5,There is a close connection between the H558R SNP and the Lone AF inHan population and the R allele probably may be pathogenic H allele May beprotective for the Lone AF.