Genetic Studies in Hispanic/Latino Populations
There have also been efforts to characterize specific ion channelopathy genetic variants in Hispanic and Latino populations. In a 2015 study, Selga et al. characterized the genetic variation of BrS in a Spanish cohort, finding 19 variations in SCN5A that could potentially contribute to pathogenicity and also found that these variants could have a higher mean pathogenicity yield in a Spanish cohort compared to other European cohorts.24 In a systematic review and meta-analysis by Kong et al., the channelopathy genes SCN5A ,NOS1AP , KCNH2 , KCNE1 , and KCNQ1 were examined among Hispanic, Black, Caucasian, and Asian ethnicities, andKCNQ1 was found to be present in the Hispanic group at the highest frequency.25 A genome-wide association study conducted by Mendez-Giraldez et al. examined QT interval prolongation in a Hispanic and Latino population, revealing six secondary signals at specific genes, including NOS1AP , ATP1B1 , SCN5A , and KCNQ1 .26 A comparison of linkage disequilibrium patterns suggested that lead single-nucleotide polymorphisms (SNPs) in SCN5A and KCNE1 might be novel and specific to the Hispanic/Latino populations.26 Another study conducted by Arking et al. on QT interval prolongation in the Hispanic/Latino demographic highlighted SNPs in NOS1AP that may be associated with an increase in QT interval.27Nonetheless, it should be noted that this study did not reach statistical significance in the Hispanic and Latino groups.27 A study by Shah et al. further examined the link between NOS1AP and QT interval change in a multi-ethnic group and found potentially significant associations in the 5’ end ofNOS1AP in the Hispanic cohort.28 In a fine-mapping study, Avery et al. discovered a significant association between QT interval prolongation and SNPs in NOS1AP ,SCN5A , and SCN10A in Hispanic/Latino participants.29
As mentioned above, while genetic variants that contribute to arrhythmogenicity and racial disparities that increase the risk of SCD have been characterized in AA/Black and Asian demographics, albeit to a limited extent, there is a need to identify similar factors in Hispanic/Latino and Indigenous populations to fully characterize ion channelopathies and SCD risk profiles in these groups. The available medical knowledge to date includes the PRESTO and HCHS/SOL study conducted by Reinier et al. to highlight risk factors for SCD in a Hispanic and Latino demographic.16 This study conducted in Ventura County, California, and the San Diego site of the Hispanic Community Health Survey/Study of Latinos is the first to assess predictors of SCD risk, specifically among Hispanic and Latino individuals in the United States. Analyzing data from 295 Hispanic and Latino SCD cases and 590 frequency-matched controls, the study identified several clinical variables associated with SCD, such as AF (Figure 2 ).16 These associations held true even after adjusting for age, sex, and other clinical variables. A review by Kiernan et al. highlighted the disproportionate effect of SCD disease burden in non-Caucasian identifying populations and racial and ethnic differences in the efficacy of implantable cardioverter-defibrillators in these groups.30 In a retrospective postmortem study on sudden explained deaths, Lin et al. utilized high-resolution variant classification in cardiac arrhythmogenic gene testing within a diverse cohort.31The study found that 3.1% of the Hispanic subjects tested positive for pathogenic or likely pathogenic arrhythmogenic genetic variants.31