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