دورية أكاديمية
أعرض في EDS

Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy.

التفاصيل البيبلوغرافية
العنوان: Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy.
المؤلفون: Mori AA; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Castro LR; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Bortolin RH; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Bastos GM; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil; Real e Benemerita Associação Portuguesa de Beneficiencia, Sao Paulo, Brazil., Oliveira VF; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Ferreira GM; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Hirata TDC; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Fajardo CM; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Sampaio MF; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil; Real e Benemerita Associação Portuguesa de Beneficiencia, Sao Paulo, Brazil., Moreira DAR; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Pachón-Mateos JC; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Correia EB; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Sousa AGMR; Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil., Brión M; Genetica Cardiovascular, Instituto de Investigación Sanitaria de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain; Grupo de Medicina Genômica, Universidad de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain., Carracedo A; Grupo de Medicina Genômica, Universidad de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain; Centro Nacional de Genotipado-CeGen-USC-PRB3-ISCIII, Santiago de Compostela, Spain., Hirata RDC; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Hirata MH; School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: mhhirata@usp.br.
المصدر: Forensic science international. Genetics [Forensic Sci Int Genet] 2021 May; Vol. 52, pp. 102478. Date of Electronic Publication: 2021 Feb 03.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101317016 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-0326 (Electronic) Linking ISSN: 18724973 NLM ISO Abbreviation: Forensic Sci Int Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier
مواضيع طبية MeSH: Mutation*, Cardiac Myosins/*genetics , Cardiomyopathy, Hypertrophic/*genetics , Carrier Proteins/*genetics , Myosin Heavy Chains/*genetics , Troponin T/*genetics, Brazil ; Death, Sudden, Cardiac/etiology ; Echocardiography ; Female ; Genetic Association Studies ; Heart Septum/diagnostic imaging ; Heterozygote ; Humans ; Male ; Middle Aged ; Risk Factors ; Sequence Analysis, DNA
مستخلص: 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.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Genetic variants; Hypertrophic cardiomyopathy; Left ventricular hypertrophy; Sarcomeric genes; Sudden cardiac death
المشرفين على المادة: 0 (Carrier Proteins)
0 (MYH7 protein, human)
0 (TNNT2 protein, human)
0 (Troponin T)
0 (myosin-binding protein C)
EC 3.6.1.- (Cardiac Myosins)
EC 3.6.4.1 (Myosin Heavy Chains)
تواريخ الأحداث: Date Created: 20210215 Date Completed: 20210805 Latest Revision: 20210805
رمز التحديث: 20231215
DOI: 10.1016/j.fsigen.2021.102478
PMID: 33588347
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-0326
DOI:10.1016/j.fsigen.2021.102478