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Identifying modifier genes for hypertrophic cardiomyopathy.
Chen, Yuanjian; Xu, Fuyi; Munkhsaikhan, Undral; Boyle, Charlie; Borcky, Theresa; Zhao, Wenyuan; Purevjav, Enkhsaikhan; Towbin, Jeffrey A; Liao, Fang; Williams, Robert W; Bhattacharya, Syamal K; Lu, Lu; Sun, Yao.
Afiliación
  • Chen Y; Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Xu F; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Munkhsaikhan U; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Boyle C; Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Borcky T; Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Zhao W; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Purevjav E; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Towbin JA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Liao F; Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Williams RW; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Bhattacharya SK; Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America.
  • Lu L; Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, United States of America. Electronic address: llu@uthsc.edu.
  • Sun Y; Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States of America. Electronic address: yasun@uthsc.edu.
J Mol Cell Cardiol ; 144: 119-126, 2020 07.
Article en En | MEDLINE | ID: mdl-32470469
BACKGROUND: Hypertrophic cardiomyopathy (HCM) severity greatly varies among patients even with the same HCM gene mutations. This variation is largely regulated by modifier gene(s), which, however, remain largely unknown. The current study is aimed to identify modifier genes using BXD strains, a large murine genetic reference population (GRP) derived from crosses between C57BL/6 J (B6) and D2 DBA/2 J (D2) mice. D2 mice natualy carrythe genetic basis and phenotypes of HCM. METHODS: Myocardial hypertrophy, the major phenotype of HCM, was determined by cardiomyocyte size on cardiac sections in 30 BXD strains, and their parental B6 and D2 strains and morphometric analysis was performed. Quantitative Trait Locus (QTL) mapping for cardiomyocyte sizes was conducted with WebQTL in GeneNetwork. Correlation of cardiomyocyte size and cardiac gene expression in BXDs accessed from GeneNetwork were evaluated. QTL candidate genes associated with cardiomyocyte sizes were prioritized based on the score system. RESULTS: Cardiomyocyte size varied significantly among BXD strains. Interval mapping on cardiomyocyte size data showed a significant QTL on chromosome (Chr) 2 at 66- 73.5 Mb and a suggestive QTL on Chr 5 at 20.9-39.7 Mb. Further score system revealed a high QTL score for Xirp2 in Chr 2. Xirp2 encodes xin actin-binding repeat containing 2, which is highly expressed in cardiac tissue and associate with cardiomyopathy and heart failure. In Chr5 QTL, Nos3, encoding nitric oxide synthase 3, received the highest score, which is significantly correlated with cardiomyocyte size. CONCLUSION: These results indicate that Xirp2 and Nos3 serve as novel candidate modifier genes for myocardial hypertrophy in HCM. These candidate genes will be validated in our future studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Predisposición Genética a la Enfermedad / Genes Modificadores Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Predisposición Genética a la Enfermedad / Genes Modificadores Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido