Genetic Study Of Ischemia-Induced Ventricular Arrhythmia Associated With Potassium Channels

Objective:Sudden cardiac death (SCD) is one of the major causes of death. Some studies implicated that ion channels play an important role in ischemia-induced malignant arrhythmias. Recent report and our preliminary research show that mutation of sodium channel gene is one of the disease-causing gene in ischemia-induced ventricular arrhythmia. In this study, candidate genes were screened for 11 potassium channels with direct sequencing to reveal the relationship between ischemia-induced ventricular arrhythmia and potassium channel mutation.Methods:23 patients with ischemia-induced ventricular tachycardia/ventricular fibrillation were selected as study subjects.5ML peripheral blood was taken from each person, from which DNA was extracted using a standard enzymatic phenol-chloroform method.11 candidate genes including HERG (KCNH2),KCNQ1 (KVLQT1),KCNE1 (Mink),KCNE2 (Mirp1),KCNJ2 (Kir2.1),KCNJ3 (Kir3.1),KCNJ8(Kir6.1),KCNJ11(Kir6.2),KCNJ12(Kir2.2),KCND3(KV4.3),KCNA5 (KV1.5) were screened with direct sequencing methods. Gene variation comparing with 100 normal control subjects ensure gene mutation or SNP.Results:Mutation from 11 potassium channels has not been found in 23 patients.10 SNP in 11 potassium channel genes (KCNJ12-G216G, KCNJ12-Q192H, KCNJ12-P156L, HERG-F513F, HERG-I489I, KV1.5-P513P, Kir2.1-L382L, Kir6.2-V337I, KCNQ1-P448R, KCNQ1-S546S) have been found. The KCNJ12-G216G is a novel SNP, which shows a change from T base to C base at the position of 1353 on the third exon of KCNJ12 gene. The rest of SNPs has been reported in NCBI-SNP-Geneview. The SNPs distribution from KCNJ12-Q192H, KCNJ12-P156L, HERG-I489I, KV1.5-P513P, Kir2.1-L382L, Kir6.2-V337I, KCNQ1-P448R and KCNQ1-S546S are similar with those reported in the NCBI-SNP-Geneview. The SNP of HERG-F513F is at the position of 1545 C base substitution T base on the seventh exon of the HERG gene.5 patients have been found the SNP of HERG-F513F while 46 normal individual in the control group. Chi-square test shows that there is a difference in the incidence of the SNP of HERG-F513F between the two groups (χ2=4.535, P<0.05).Conclusion:No potassium channel genes mutation has been found in our study, However, a novel SNP of KCNJ12-G216G was discovered in Chinese people. The SNP of HERG-F513F might be a predisposing factor in ischemia-induced ventricular arrhythmia.