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Genetic and functional variants of the TBX20 gene promoter in dilated cardiomyopathy.
Gao, Xue; Pang, Shuchao; Ding, Liangcai; Yan, Han; Cui, Yinghua; Yan, Bo.
Afiliação
  • Gao X; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
  • Pang S; The Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
  • Ding L; Shandong Provincial Sino-US Cooperation Research Center for Translational Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
  • Yan H; Center for Molecular Medicine, Yanzhou People's Hospital, Jining Medical University, Jining, Shandong, China.
  • Cui Y; Center for Molecular Medicine, Yanzhou People's Hospital, Jining Medical University, Jining, Shandong, China.
  • Yan B; Division of Cardiology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
Mol Genet Genomic Med ; 12(1): e2355, 2024 Jan.
Article em En | MEDLINE | ID: mdl-38284443
ABSTRACT

BACKGROUND:

Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death. As DCM is a genetically heterogeneous disease, genetic variants of cardiac transcription factor genes may play an important role. Transcription factor TBX20, an indispensable factor in normal heart development, is involved in the regulation of cardiac structure and function. Although the TBX20 gene is associated with the occurrence and development of DCM, the influence of genetic variants of the TBX20 gene promoter region on DCM has not been reported.

METHODS:

We conducted a case-control study consisting of 107 DCM patients and 210 healthy controls. Genetic variants within TBX20 gene promoter region were identified using sequencing techniques and were functionally analyzed by dual-luciferase reporting assay. Electrophoretic mobility shift assay (EMSA) was used to investigate DNA-protein interactions.

RESULTS:

In this study cohort (n = 317), we identified eight variants within TBX20 gene promoter. One novel DNA sequence variants (DSV) (g.4275G>T) and four single-nucleotide polymorphisms (SNPs) [g.4169G>A (rs1263874255), g.4949C>T (rs1191745927), g.5114G>A (rs112076877), g.5252C>T (rs1356932911)] were identified in DCM patients, but in none of controls. Among them, the DSV (g.4275G>T) and three SNPs [g.4949C>T (rs1191745927), g.5114G>A (rs112076877) and g.5252C>T (rs1356932911)] significantly altered the transcription activity of TBX20 gene promoter by dual-luciferase reporting assay (p < 0.05). Further, EMSA assay indicated that the DSV (g.4275G>T) and three SNPs [g.4949C>T (rs1191745927), g.5114G>A (rs112076877) and g.5252C>T (rs1356932911)] affected the binding of transcription factors.

CONCLUSIONS:

These data indicate that the DSV (g.4275G>T) and three SNPs [g.4949C>T (rs1191745927), g.5114G>A (rs112076877) and g.5252C>T (rs1356932911)] increase transcription activity of TBX20 gene promoter in both HEK-293 and neonatal rat cardiomyocytes (NRCMs) cell lines by affecting the binding of transcription factors. But the mechanism remains to be verified in vivo.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 6_ODS3_enfermedades_notrasmisibles / 7_ODS3_muertes_prevenibles_nacidos_ninos Base de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Proteínas com Domínio T Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mol Genet Genomic Med Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 / 6_ODS3_enfermedades_notrasmisibles / 7_ODS3_muertes_prevenibles_nacidos_ninos Base de dados: MEDLINE Assunto principal: Cardiomiopatia Dilatada / Proteínas com Domínio T Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Mol Genet Genomic Med Ano de publicação: 2024 Tipo de documento: Article