Ethnic Differences in Genetic Ion Channelopathies Associated with Sudden Cardiac Death: A Systematic Review and Meta-Analysis

Background and aims: Reports of allele frequencies encoding ion channel, or their interacting proteins associated with sudden cardiac death among different ethnic groups have been inconsistent. Here, we aimed to characterize the distribution of these genes and their alleles among various ethnicities through meta-analysis.

Methods: We conducted a systematic review and meta-analysis to assess the mean allele frequencies of channelopathy genes SCN5A, NOS1AP, KCNH2, KCNE1, and KCNQ1 among the Black, Caucasian, Asian, and Hispanic ethnicities. Searches in PubMed, Google Scholar, and Web of Science resulted in 18 reports published before July 2015 that met the eligible criteria. Allele frequencies were averaged by weight, and pooled values were calculated by inverse variance. Fixed-effects and random-effects models were used to pool effect sizes within each study and across different studies, respectively. Moreover, to extend our findings, we used sequenced genomic data from the Exome Aggregation Consortium to compare allele frequencies between different ethnicities.

Results: Meta-analysis of published studies supports that Asians had the highest overall mean allele frequencies of NOS1AP (0.36%, 95% CI: 0.30, 0.43; P<0.001), and SCN5A frequencies (0.17%, 95% CI: 0.07, 0.27, P=0.001), and whereas Caucasians had the highest KCNH2 frequency (0.21%, 95% CI: 0.16, 0.25; P<0.001), and Hispanics the highest KCNQ1 frequency (0.16%). Analysis of the Exome Aggregation Consortium also provided consistent data in agreement the meta-analysis.

Conclusion: Overall, Asians carried the most alleles of genes associated with sudden cardiac death. The meta-analysis reveals significant differences in allele distribution of channelopathy-associated genes among different ethnic groups.