Jie Wang, Dominic Russ, Yongsan Yang, Lutong Pu, Mengdi Yu, Jinquan Zhang, Jiajun Guo, Yuanwei Xu, Ke Wan, Heng Xu, Yuchi Han, Georgios V Gkoutos, Yucheng Chen
{"title":"Genetic architecture of hypertrophic cardiomyopathy in individuals of Chinese and United Kingdom ancestry.","authors":"Jie Wang, Dominic Russ, Yongsan Yang, Lutong Pu, Mengdi Yu, Jinquan Zhang, Jiajun Guo, Yuanwei Xu, Ke Wan, Heng Xu, Yuchi Han, Georgios V Gkoutos, Yucheng Chen","doi":"10.1093/pcmedi/pbaf019","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy (HCM) populations.</p><p><strong>Methods: </strong>This cross-sectional study included Chinese patients (<i>n</i> = 593) with HCM and controls (<i>n</i> = 491) who underwent whole-exome sequencing. Rare variants in 16 validated HCM genes were assessed and compared with a United Kingdom HCM cohort (<i>n</i> = 1 232) and controls (<i>n</i> = 344 745).</p><p><strong>Results: </strong>Chinese HCM patients have a higher proportion of rare variants (52.8% vs 13.6%, <i>P</i> < 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 (<i>P</i> = 1.29E-9) and myosin light chain genes (<i>P</i> = 4.43E-3). The United Kingdom cohort was significantly associated with <i>MYBPC3</i> non-truncating variants (<i>P</i> = 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 <i>MYBPC3</i> and c.300C > G in <i>TNNT2</i> account for 2.9% and 1.5% of all Chinese HCM cases, respectively.</p><p><strong>Conclusion: </strong>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 <i>MYBPC3</i> and c.300C > G in <i>TNNT2</i> were specific to Chinese individuals and provide important insights into the ethnic differences of HCM genetic architecture.</p>","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"8 3","pages":"pbaf019"},"PeriodicalIF":5.0000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375896/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Precision Clinical Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/pcmedi/pbaf019","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Precision Clinical Medicine (PCM) is an international, peer-reviewed, open access journal that provides timely publication of original research articles, case reports, reviews, editorials, and perspectives across the spectrum of precision medicine. The journal's mission is to deliver new theories, methods, and evidence that enhance disease diagnosis, treatment, prevention, and prognosis, thereby establishing a vital communication platform for clinicians and researchers that has the potential to transform medical practice. PCM encompasses all facets of precision medicine, which involves personalized approaches to diagnosis, treatment, and prevention, tailored to individual patients or patient subgroups based on their unique genetic, phenotypic, or psychosocial profiles. The clinical conditions addressed by the journal include a wide range of areas such as cancer, infectious diseases, inherited diseases, complex diseases, and rare diseases.
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