East Asian-Specific Common Variant in Predisposes to Hypertrophic Cardiomyopathy.

Keywords: Asians; cardiomyopathy, hypertrophic; genetic testing; hypertrophy EN Asians cardiomyopathy, hypertrophic genetic testing hypertrophy 2086 2089 4 11/25/20 20201124 NES 201124 Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder characterized by unexplained left ventricular hypertrophy.[1] Although considered as a dominant Mendelian disease mainly caused by rare pathogenic variants in sarcomere genes, the genetic underpinnings of nearly half of patients remain unsolved.[2] Increasing evidence implies that HCM has a more complex genetic architecture.[3] We identified an East Asian-specific common missense variant in I TNNI3 i (rs3729712) associated with HCM in an exome-wide case-control association study of Chinese origin and replicated the finding in 3 independent studies ( I P i =5.80×10 SP -22 sp ). The association was confirmed in each of the 3 replication studies, among which the Beijing replication samples and Xi'an-1 cases were genotyped by a panel sequencing of cardiomyopathy candidate genes, and the Xi'an-1 controls and Xi'an-2 samples by Sanger sequencing. Patients with HCM were classified into SARC+ (pathogenic or likely pathogenic variant identified in a sarcomere gene) and SARC- (no potentially pathogenic variant identified in a sarcomere gene) groups by the presence of any variant of pathogenic, likely pathogenic, or unknown significance in the 8 sarcomere genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, and ACTC1) in the discovery study (495 vs 491), Beijing replication study (226 vs 303), and Xi'an-1 study (342 vs 304). [Extracted from the article]