Abstract
Background: No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy (HCM) populations.
Methods: This cross-sectional study included Chinese patients (n = 593) with HCM and controls (n = 491) who underwent whole-exome sequencing. Rare variants in 16 validated HCM genes were assessed and compared with a United Kingdom HCM cohort (n = 1 232) and controls (n = 344 745).
Results: Chinese HCM patients have a higher proportion of rare variants (52.8% vs 13.6%, P < 0.001) but have a similar proportion of pathogenic (P) or likely pathogenic (LP) variants compared to the UK cohort. In addition, the Chinese cohort had additional associations with the combined thin filament genes (P = 1.29E-9) and myosin light chain genes (P = 4.43E-3). The United Kingdom cohort was significantly associated with MYBPC3 non-truncating variants (P = 2.99E-7). By classifying variants using the tool genebe, the variants of uncertain significance were minimized to 46.8% compared to other tools (63.3% by Intervar; 91.3% by CardioClassifier). Furthermore, we report that c.3624del in MYBPC3 and c.300C > G in TNNT2 account for 2.9% and 1.5% of all Chinese HCM cases, respectively.
Conclusion: Our findings suggested that patients of Chinese ancestry with HCM have a higher proportion of rare variants but are less likely to be classified as P/LP variants in HCM genes than those of European origin. The variants of c.3624del in MYBPC3 and c.300C > G in TNNT2 were specific to Chinese individuals and provide important insights into the ethnic differences of HCM genetic architecture.