Association Between The SCN5A Gene And Non-valvular Atrial Fibrillation In The Region Of Ethnic Minorities

Objective: The study mainly investigate the relevantion between SCN5 A gene and patients with non-valvular atrial fibrillation.Methods: ⑴100 patients were selected for non-valvular atrial fibrillation and 110 patients with non-atrial fibrillation for controls from the region of Ethnic minorities.⑵The clinical data,blood samples,and peripheral blood DNA were collected.The case-group-specific single nucleotide variants(SNV)obtained by sequencing were compared with GWAS database,db SNP database,Thousand Genome database,ESP exome database,Yanhuang genome database,etc,and screened for rare or new occurrence of SCN5 A Mutation and further verification by sanger sequencing.Results: ⑴In both Ethnic and Han populations,Probands had statistical significance in age,hypertension,smoking,uric acid,total cholesterol,lactate dehydrogenase,platelet(P <0.05),but heavy,gender,diabetes,low density lipoprotein,and white blood cells were no statistically significant difference(P> 0.05).There were also significant difference in age,gender,uric acid,total cholesterol platelet between the Han cases with controls,(P <0.05),but weight,hypertension,smoking,low-density lipoprotein,lactate dehydrogenase,white blood cells and diabetes were no statistically significant difference(P> 0.05).Compared with the controls,AF of the minority had statistically significant differences in age,weight,uric acid,total cholesterol,low-density lipoprotein,lactate dehydrogenase,white blood cell and platelet(P <0.05),the difference was not statistically significant in gender,hypertension,diabetes,and smoking(P> 0.05).The difference was not statistically significant in age,weight,gender,hypertension,diabetes,smoking,uric acid,total cholesterol,low density lipoprotein,lactate dehydrogenase,white blood cells,and platelet between the minority AF sick people and the Han AF populations(P> 0.05).⑵Analysis of logistic regression model showed that weight,total cholesterol platelet were independent risk factors of AF(OR = 2.238,1.987,1.117;P = 0.084,0.648,0.072,0.187).In minority AF populations,the results showed that total cholesterol was an independent risk factor for AF(OR = 1.186;P = 0.606).ROC curve analysis showed that the AUC of age,uric acid,platelet and lactate dehydrogenase were 0.663,0.643,0.341,0.742,predictive value LDH> age> UA> PT(P <0.001).In the comparison between the minority AF groups and the Han AF groups,the results showed that age,gender,uric acid,and low-density lipoprotein were independent risk factors of AF(OR = 1.026,1.848,1.010,1.060;P = 0.192,0.200,0.431,0.780).⑶Four missense mutations were screened out AF,R965 C,P1090L was a newly discovered mutation and R965 C was predicted to be a harmful mutation by using SIFT and Poly Phen-2 software.H558 R and R1193 Q missense mutations are frequent polymorphisms.Four missense mutant amino acids are located in the highly conserved region of the SCN5 A protein.⑷The genotypes and allele frequencies of H558 R and R1193 Q were statistically significant in the minority group AF groups and the control groups(P <0.05).The allele frequency of the R1193 Q was statistically significant between the AF and the controls of the Han populations(P <0.05).The genotypes and allele frequencies of H558 R were statistically significant in the minority AF populations and the Han AF populations(P <0.05).⑸Multivariate logistic regression analysis of the SCN5 A gene H558 R revealed that the risk factors for atrial fibrillation found that the G allele in the Han population may be an independent risk factor of AF(OR = 1.363,P = 0.551),and in the minority populations,the G allele It may be an independent risk factor for AF(OR = 6.020,P = 0.005).In the general population,it is also confirmed that the G allele may be an independent risk factor for AF(OR = 2.646,P = 0.009).⑹The SCN5 A gene H558 R genotype and allele frequency were statistically significant in the AF of ethnic minority areas and other ethnic and regional populations(P <0.01).The genotypes of the R1193 Q locus were statistically different between the AF in minority areas and those in global,Africa,Europe,and South Asia(P <0.05),while the allele frequency were statistically significant for AF between minority areas and Africa,Europe,South Asia,and America(P <0.05).Conclusion: ⑴This study shows that the SCN5 A R965C mutation may be a risk factor for the development of AF in the region of Ethnic minorities.⑵SCN5A gene H558 R,R1193Q polymorphism S may be a genetic susceptibility factor for AF.⑶The distribution characteristics of the SCN5 A gene H558 R polymorphism are different between the minority population AF and the Han population AF,indicating that the G allele may be an important risk factor for the occurrence of atrial fibrillation in the minority ethnic groups and the Han populations,The distribution characteristics of loci polymorphism are different between the ethnic minority areas in the region of Ethnic minorities and the population in different areas.In summary,the scope of SCN5 A mutation was expanded to provide genetic counseling for AF of arrhythmia.