In:
Cardiology, S. Karger AG, Vol. 145, No. 1 ( 2020), p. 38-45
Abstract:
〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. About half of sudden deaths from AMI are mainly because of malignant ventricular arrhythmias (VA) after AMI. The sodium channel gene 〈 i 〉 SCN5A 〈 /i 〉 and potassium channel genes 〈 i 〉 KCNQ1 〈 /i 〉 and 〈 i 〉 KCNH2 〈 /i 〉 have been widely reported to be genetic risk factors for arrhythmia including Brugada syndrome and long QT syndrome (LQTS). A few studies reported the association of 〈 i 〉 SCN5A 〈 /i 〉 variant with ventricular tachycardia (VT)/ventricular fibrillation (VF) complicating AMI. However, little is known about the role of 〈 i 〉 KCNQ1 〈 /i 〉 and 〈 i 〉 KCNH2 〈 /i 〉 in AMI with VA (AMI_VA). This study focuses on investigating the potential variants on 〈 i 〉 SCN5A 〈 /i 〉 , 〈 i 〉 KCNQ1 〈 /i 〉 , and 〈 i 〉 KCNH2 〈 /i 〉 contributing to AMI with VA in a Chinese population. 〈 b 〉 〈 i 〉 Materials and Methods: 〈 /i 〉 〈 /b 〉 In total, 139 patients with AMI_VA, and 337 patients with AMI only, were included. Thirty exonic sites were selected to be screened. Sanger sequencing was used to detect variants. A subsequent association study was also performed between AMI_VA and AMI. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Twelve variants [5 on 〈 i 〉 KCNH2 〈 /i 〉 ( 〈 i 〉 NM_000238.3 〈 /i 〉 ), 3 on 〈 i 〉 KCNQ1 〈 /i 〉 ( 〈 i 〉 NM_000218.2 〈 /i 〉 ), and 4 on 〈 i 〉 SCN5A 〈 /i 〉 ( 〈 i 〉 NM_198056.2 〈 /i 〉 )] were identified in AMI_VA patients. Only 5 ( 〈 i 〉 KCNH2 〈 /i 〉 : c.2690A & #x3e;C; 〈 i 〉 KCNQ1 〈 /i 〉 : c.1927G & #x3e;A, c.1343delC; 〈 i 〉 SCN5A 〈 /i 〉 : c.1673A & #x3e;G, c.3578G & #x3e;A) of them are missense variants. Two ( 〈 i 〉 KCNQ1 〈 /i 〉 : c.1343delC and 〈 i 〉 SCN5A 〈 /i 〉 : c.3578G & #x3e;A) of the missense variants were predicted to be clinically pathogenic. All these variants were further genotyped in an AMI without VA group. The association study identified a statistically significant difference in genotype frequency of 〈 i 〉 KCNH2 〈 /i 〉 : c.1539C & #x3e;T and 〈 i 〉 KCNH2 〈 /i 〉 : c.1467C & #x3e;T between the AMI and AMI_VA groups. Moreover, 2 rare variants ( 〈 i 〉 KCNQ1 〈 /i 〉 : c.1944C & #x3e;T and 〈 i 〉 SCN5A 〈 /i 〉 : c.3621C & #x3e;T) showed an elevated allelic frequency (more than 1.5-fold) in the AMI_VA group when compared to the AMI group. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Twelve variants (predicting from benign/VUS to pathogenic) were identified on 〈 i 〉 KCNH2 〈 /i 〉 , 〈 i 〉 KCNQ1 〈 /i 〉 , and 〈 i 〉 SCN5A 〈 /i 〉 in patients with AMI_VA. Genotype frequency comparison between AMI_VA and AMI identified 2 significant common variants on 〈 i 〉 KCNH2 〈 /i 〉 . Meanwhile, the allelic frequency of 2 rare variants on 〈 i 〉 KCNQ1 〈 /i 〉 and 〈 i 〉 SCN5A 〈 /i 〉 , respectively, were identified to be enriched in AMI_VA, although there was no statistical significance. The present study suggests that the ion-channel genes 〈 i 〉 KCNH2 〈 /i 〉 , 〈 i 〉 KCNQ1 〈 /i 〉 , and 〈 i 〉 SCN5A 〈 /i 〉 may contribute to the pathogenesis of VA during AMI.
Type of Medium:
Online Resource
ISSN:
0008-6312
,
1421-9751
Language:
English
Publisher:
S. Karger AG
Publication Date:
2020
detail.hit.zdb_id:
1482041-9
