Abstract P2104: Prevalence of Hypertrophic Cardiomyopathy Core Gene Variants in Hispanics/Latinos: A Study from The Hispanic Community Health Study / Study of Latinos (HCHS-SOL)

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM) is an inherited disease associated with genetic variants in sarcomeric genes, mostly studied in White populations. There is a paucity of literature, especially Hispanics/Latinos (H/L) populations where HCM sarcomeric variant prevalence is unknown. Methods: We analyzed whole-genome sequencing data from the Hispanic Community Health Study to assess sarcomeric variants in a diverse H/L sample. We identified HCM variant carriers based on eight sarcomeric genes (MYBPC3, MYH7, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Carriers were defined according to predictions from the HumDiv model of PolyPhen-2, by having at least one nonsynonymous deleterious (category D) variant. The prevalence of HCM genetic carrier was estimated accounting for complex survey design. Sociodemographic and clinical variables were analyzed across HCM variant carrier/non-carrier carrier status, with sampling weights used to calculate weighted means, frequencies, and population estimates. Results: Among 7,724 individuals self-identified as H/L, the overall prevalence of HCM variant carrier was 6.08%. The most commonly detected variants were on MYBPC3 and MYH7 while ACTC1 was not observed. (Figure 1. A) HCM variant carriers had a mean age of 41.20 ± 1.00 years, 50.32% were female, and the mean BMI was 30.13 ± 0.36 kg/m^2. There was no difference in burden of comorbidities among carriers and non-carriers. HCM variant carrier status was more likely among the H/L of Dominican descent than any other H/L background group (p<0.001). (Figure 1. B) Conclusions: The prevalence of HCM sarcomeric variants among H/L individuals was higher than previously reported in non-Hispanic populations. Among H/L, MYH7 and MYBPC3 were the most common, consistent with previous reports in non-Hispanic populations. HCM variant carrier prevalence varied across Hispanic background groups, likely due to different makeup of genetic ancestries. Our results identify the H/L population at possible elevated risk for developing clinical HCM, underscoring the need for inclusion of H/L in ongoing studies of HCM evaluation and management strategies. Authors: Jorge Silva Enciso and Reniell Iñiguez are co-first authors.