Associations between common ion channel single nucleotide polymorphisms and sudden cardiac death in adults: A MOOSE-compliant meta-analysis

Medicine (Baltimore). 2018 Sep;97(38):e12428. doi: 10.1097/MD.0000000000012428.

Abstract

Background: We sought to identify common ion channel single nucleotide polymorphisms (SNPs) associated with the occurrence of sudden cardiac death (SCD) to predict the incidence of SCD in clinical settings.

Methods: This study involved a systematic review and meta-analysis of ion channel SNPs and risk of SCD in adults. We searched public databases for studies published up to September 19, 2017. We examined relationships between SNPs in common ion channel genes and the incidence of SCD.

Results: We collected data for 22 trials that included a total of 4149 patients who experienced SCD or had a high risk of SCD and assessed these data in our meta-analysis. An allelic model showed that rs11720524 in SCN5A clearly protected against SCD (odds ratio [OR]: 0.76; 95% confidence interval [95% CI]: 0.67-0.85; P < .001). Subgroup analysis showed that rs11720524 in SCN5A protected against SCD in Europeans and Caucasians but not in Koreans. The allelic model indicated that rs12296050 in KCNQ1 also had significant protective effects against SCD (OR: 0.85; 95% CI: 0.76-0.96; P = .007). Moreover, this model demonstrated that rs2283222 in KCNQ1 had a significant negative relationship with SCD (OR: 0.73; 95% CI: 0.62-0.85; P < .001). Rs12296050 in KCNQ1 protected against SCD in Koreans and Americans. Our results also showed that rs790896 in RYR2 was negatively associated with SCD in a dominant model (OR: 0.66; 95% CI: 0.45-0.97; P = .033).

Conclusions: Rs11720524 in SCN5A is negatively related to SCD in Europeans and Caucasians, and rs12296050 and rs2283222 in KCNQ1 and rs790896 in RYR2 clearly have protective effects against SCD.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Alleles
  • Asian People / genetics
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / ethnology
  • Death, Sudden, Cardiac / etiology
  • Female
  • Humans
  • Incidence
  • Ion Channels / genetics*
  • KCNQ1 Potassium Channel / genetics
  • Male
  • NAV1.5 Voltage-Gated Sodium Channel / genetics
  • Observational Studies as Topic
  • Polymorphism, Single Nucleotide / genetics*
  • Predictive Value of Tests
  • Ryanodine Receptor Calcium Release Channel / genetics
  • White People / genetics

Substances

  • Ion Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • RyR2 protein, human
  • Ryanodine Receptor Calcium Release Channel
  • SCN5A protein, human