Abstract
Coronary artery disease (CAD) and its ultimate consequence - myocardial infarction (MI) - are major causes of sudden cardiac death (SCD). Previous studies have demonstrated the role of genetic polymorphisms in the risk of SCD and ventricular arrhythmia (VA) during MI. To investigate the association between single nucleotide polymorphisms (SNPs) of genes implicated in congenital cardiac arrhythmias and the risk of developing VA in the context of MI. We performed a case-control study in which we genotyped 4 SNPs (rs11708996, rs10428132, rs9388451, and rs2200733) in 469 subjects using amplification refractory mutation system (ARMS) and a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These SNPs are located in the SCN5A, SCN10A, HEY2, and PITX2 genes, respectively. We first compared 70 patients who had developed VA in the context of MI with 141 healthy controls; next, we compared VA patients with 258 MI patients who did not develop VA during a 1-year follow up. The statistical analyses were adjusted for sex and age. Compared to the controls, 2 polymorphisms were significantly associated with the development of VA during MI, located in SCN5A rs11708996 (p = 0.001) and SCN10A rs10428132 (p = 0.001). Similar results were found when comparing VA cases with patients without VA. No associations of HEY2 and PITX2 polymorphisms were observed. Our results suggest that the rs11708996 and rs10428132 polymorphisms of the SCN5A and SCN10A genes may contribute to an elevated risk of developing VA in the context of MI. The associated alleles or genotypes may be used to predict the risk, and thus prevent eventual SCD.
Highlights
In the last decade, there have been notable advances in the study of the mechanisms responsible for increased risk of arrhythmia and sudden cardiac death (SCD)
2 polymorphisms were significantly associated with the development of ventricular arrhythmia (VA) during myocardial infarction (MI), located in SCN5A rs11708996 (p = 0.001) and SCN10A rs10428132 (p = 0.001)
Our results suggest that the rs11708996 and rs10428132 polymorphisms of the SCN5A and SCN10A genes may contribute to an elevated risk of developing VA in the context of MI
Summary
There have been notable advances in the study of the mechanisms responsible for increased risk of arrhythmia and sudden cardiac death (SCD). In 5–10% of all cases, SCD occurs in patients with congenital rhythm disorders with normal heart structure.[1]. SCD is mainly described in the setting of structural heart disease resulting from ventricular arrhythmias (VA), ventricular fibrillation (VF). Ventricular arrhythmia most commonly occurs early in ischemia, and patients presenting acute myocardial infarction (MI) and VA show a high risk of mortality.[2,3]. Coronary artery disease (CAD) and its ultimate consequence − myocardial infarction (MI) − are major causes of sudden cardiac death (SCD). Previous studies have demonstrated the role of genetic polymorphisms in the risk of SCD and ventricular arrhythmia (VA) during MI
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