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Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy
Mori, Augusto Akira; Castro, Lara Reinel de; Bortolin, Raul Hernandes; Bastos, Gisele Medeiros; Oliveira, Victor Fernandes de; Ferreira, Glaucio Monteiro; Hirata, Thiago Dominguez Crespo; Fajardo, Cristina Moreno; Sampaio, Marcelo Ferraz; Moreira, Dalmo Antonio Ribeiro; Pachón-Mateos, José Carlos; Correia, Edileide de Barros; Sousa, Amanda Guerra de Moraes Rego; Brión, Maria; Carracedo, Angel; Hirata, Rosario Dominguez Crespo; Hirata, Mario Hiroyuki.
Afiliação
  • Mori, Augusto Akira; University of São Paulo. São Paulo. BR
  • Castro, Lara Reinel de; Dante Pazzanese of Cardiology. São Paulo. BR
  • Bortolin, Raul Hernandes; University of São Paulo. São Paulo. BR
  • Bastos, Gisele Medeiros; Dante Pazzanese of Cardiology. São Paulo. BR
  • Oliveira, Victor Fernandes de; University of São Paulo. São Paulo. BR
  • Ferreira, Glaucio Monteiro; Dante Pazzanese of Cardiology. University of São Paulo. São Paulo. BR
  • Hirata, Thiago Dominguez Crespo; University of São Paulo. São Paulo. BR
  • Fajardo, Cristina Moreno; University of São Paulo. São Paulo. BR
  • Sampaio, Marcelo Ferraz; Dante Pazzanese of Cardiology. São Paulo. BR
  • Moreira, Dalmo Antonio Ribeiro; Dante Pazzanese of Cardiology. São Paulo. BR
  • Pachón-Mateos, José Carlos; Dante Pazzanese of Cardiology. São Paulo. BR
  • Correia, Edileide de Barros; Dante Pazzanese of Cardiology. São Paulo. BR
  • Sousa, Amanda Guerra de Moraes Rego; Dante Pazzanese of Cardiology. São Paulo. BR
  • Brión, Maria; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER). Universidad de Santiago de Compostela. Santiago de Compostela. ES
  • Carracedo, Angel; Centro Nacional de Genotipado-CeGen-USC-PRB3-ISCIII. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER). Santiago de Compostela. ES
  • Hirata, Rosario Dominguez Crespo; University of São Paulo. São Paulo. BR
  • Hirata, Mario Hiroyuki; University of São Paulo. São Paulo. BR
Artigo em Inglês | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1247609
Biblioteca responsável: BR79.1
ABSTRACT
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is one of the major causes of sudden cardiac death (SCD). An exon-targeted gene sequencing strategy was used to investigate the association of functional variants in sarcomeric genes (MYBPC3, MYH7 and TNNT2) with severe LVH and other SCD-related risk factors in Brazilian HCM patients. Clinical data of 55 HCM patients attending a Cardiology Hospital (Sao Paulo city, Brazil) were recorded. Severe LVH, aborted SCD, family history of SCD, syncope, non-sustained ventricular tachycardia and abnormal blood pressure in response to exercise were evaluated as SCD risk factors. Blood samples were obtained for genomic DNA extraction and the exons and untranslated regions of the MYH7, MYBPC3 and TNNT2 were sequenced using Nextera® and MiSEq® reagents. Variants were identified and annotated using in silico tools, and further classified as pathogenic or benign according to the American College of Medical Genetics and Genomics guidelines. Variants with functional effects were identified in MYBPC3 (n = 9), MYH7 (n = 6) and TNNT2 (n = 4). The benign variants MYBPC3 p.Val158Met and TNNT2 p.Lys263Arg were associated with severe LVH (p < 0.05), and the MYH7 p.Val320Met (pathogenic) was associated with family history of SCD (p = 0.037). Increased risk for severe LVH was found in carriers of MYBPC3 Met158 (c.472 A allele, OR = 13.5, 95% CI = 1.80-101.12, p = 0.011) or combined variants (MYBPC3, MYH7 and TNNT2 OR = 12.39, 95% CI = 2.14-60.39, p = 0.004). Carriers of TNNT2 p.Lys263Arg and combined variants had higher values of septum thickness than non-carriers (p < 0.05). Molecular modeling analysis showed that MYBPC3 158Met reduces the interaction of cardiac myosin-binding protein C (cMyBP-C) RASK domain (amino acids Arg215-Ala216-Ser217-Lys218) with tropomyosin. In conclusion, the variants MYBPC3 p.Val158Met, TNNT2 p.Lys263Arg and MYH7 p.Val320Met individually or combined contribute to the risk of sudden cardiac death and other outcomes of hypertrophic cardiomyopathy.
Assuntos

Texto completo: Disponível Coleções: Bases de dados nacionais / Brasil Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: CONASS / Sec. Est. Saúde SP / SESSP-IDPCPROD Assunto principal: Cardiomiopatia Hipertrófica / Morte Súbita Cardíaca / Hipertrofia Ventricular Esquerda / Variantes Farmacogenômicos Tipo de estudo: Estudo de etiologia / Guia de prática clínica / Estudo prognóstico / Fatores de risco País/Região como assunto: América do Sul / Brasil Idioma: Inglês Revista: Forensic science international. Genetics (Online) Ano de publicação: 2021 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados nacionais / Brasil Contexto em Saúde: 6_ODS3_enfermedades_notrasmisibles Base de dados: CONASS / Sec. Est. Saúde SP / SESSP-IDPCPROD Assunto principal: Cardiomiopatia Hipertrófica / Morte Súbita Cardíaca / Hipertrofia Ventricular Esquerda / Variantes Farmacogenômicos Tipo de estudo: Estudo de etiologia / Guia de prática clínica / Estudo prognóstico / Fatores de risco País/Região como assunto: América do Sul / Brasil Idioma: Inglês Revista: Forensic science international. Genetics (Online) Ano de publicação: 2021 Tipo de documento: Artigo