Association Between Single Nucleotide Polymorphisms Of SCN5A Gene And Sudden Cardiac Death

【Background】Sudden cardiac death (SCD) is a tragic and devastating complication of a number ofcardiovascular diseases. Although coronary artery disease accounts for a majority of thesedeaths across all ages, many other aetiologies contribute to this problem when it occurs inthe young (age<35years), where coronary artery disease is far less common. Specifically,genetic heart disorders are an important cause of SCD in the young.Over the last decade, significant advances have been made in understanding both theclinical and genetic basis of sudden cardiac death. Many of the causes of sudden death,especially in the young, are due to genetic heart disorders, which can be broadlycategorized into those in which structural abnormalities are prominent, such asHypertrophic Cardiomyopathy and Arrhythmo-genic Right Ventricular Cardiomyopathy, ordiseases in which there is a primary arrhythmogenic abnormality, which include long QTsyndrome, Brugada syndrome, Catecholaminergic polymorphic ventricular tachycardia andshort QT Syndrome. Such cases in which no abnormalities are found at post mortem areclassified as being of unknown aetiology or unas-certained, resulting in anunderestimation of the incidence of arrhythmogenic causes of SCD. Compounding thisunderestimate, primary arrhythmogenic disorders can predispose to more overt causes ofdeath.The SCN5A gene encoding a voltage-gated sodium channel is predominatelyexpressed in the heart, where it has a key role in the generation and propagation of thecardiac impulse. SCN5A mutations have been associated with a variety of arrhythmic disorders, including type3long QT syndrome (LQT3), Brugada syndrome and inheritedcardiac conduction defects. LQT3and Brugada syndrome is an important research area ofour forensic pathological study of sudden cardiac death. SCN5A has become the hot spotsof all disciplines including forensic science. Previous studies have demonstrated not onlySCN5A mutation can lead to some common cardiac arrhythmia, but SCN5A gene singlenucleotide polymorphism loci, can also cause cardiac Na+channel disease phenotypechanges or increase of arrhythmia geneticsusceptibility. In2002,Splawski et al reported apolymorphic point Y1102in SCN5A in African Americans. Allen Burke found that thepolymorphism loci Y1102of SCN5A was risk factors of the unexplain SCD in AfricanAmericans (normal heart or mild-moderate hypertrophy). The large number of studies haveshown that the SNP was the difference in all races and regions. Caucasians and Asians wasin the detection of the polymorphic loci Y1102of SCN5A. This study aims to understandthe correlation of the SCN5A gene polymorphisms with unexpla ined SCD. UnexplainedSCD, usually physical health, sudden death without any warning symptoms, such cases wasusually related to disputes, determining the cause of death and manner of great significancefor forensic work，therefore, to determine the cause and manner of death was greatsignificance for forensic work. In addition, it has been recognized that the diseases lead toSCD were mostly hereditary, genetic testing for SCD and related family members can be aclear cause of death and to find risk factors. Genetic testing can assess the risk of thefamilies and prevent sudden death happen again.【purpose】To investigate the possible association between polymorphisms of SCN5A gene andSCD.【Materials and methods】A case-control design was applied in this study. All samples came from ForensicMedicine Department, Tongji Medical College, HUST. The samples of case group camefrom the autopsies at the Teaching and Research Section of Forensic Pathology, Thesamples of control group came from the Teaching and Research Section ofForensic Serology. The case group had34samples, identified as young SCD by means of systematic forensic pathologyical inspection and case investigation while control group had50cases of healthy people。All samples of individuals came from Hubei Province andHenan Province. The genomic DNA of case group was extracted from formalin-fixed,paraffin embedded tissue (FF-PET)。The genomic DNA of control group was extractedfrom blood。Two SNPs of SCN5A gene H558R、C5457T(D1819D) was genotyped byrestriction fragment length Polymorphism(RFLP) in all subjects. All data are presented asmean value士standard of the mean. The significance of differences between groups wasassessed using Chi-square test. Unvaried analysis was applied to measure the association ofsingle polymorphism with SCD. Binary logistic regression was performed to investigate theindependent effect between the gene type of the polymorphisms and SCD. Statisticallysignificant difference was defined as P<0.05. All analyses were performed using theSPSS18.0statistical software.【Result】1.The rare all ele frequencies of SCN5A A1673G(H558R) and C5457T (D1819D) inhealthy people of China were9.0%,39.0%.2. By univariate analysis of the two SNP loci in the frequency of young SCD group andcontrol group, we found that the difference of genotype frequency of polymorphismA1673G (H558R) was significant (P=0.04) in the two groups.【Conclusion】The study suggested existence of A1673G (H558R) polymorphisms of SCN5A genemight be related to SCD in healthy people of China. The H allele may be protective，whilethe R allele may be susceptibility gene for SCD.