Complex interactions between p.His558Arg and linked variants in the sodium voltage-gated channel alpha subunit 5 (Na(V)1.5)

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Lopes-Marques, M (Autor) Outra; Silva, R (Autor) Outra; Serrano, C (Autor) Outra; Gomes, V (Autor) Outra; Cardoso, A (Autor) Outra; Prata, MJ (Autor) FCUP; Amorim, A (Autor) FCUP; Luisa Azevedo (Autor) ICBAS

Revista

Título: PeerJ

Vol. 10

ISSN: 2167-8359

Editora: PeerJ

Indexação

ISI Web of Knowledge - 0 Citações

Scopus

Outras Informações

ID Authenticus: P-00X-228

DOI: 10.7717/peerj.13913

Abstract (EN): Common genetic polymorphisms may modify the phenotypic outcome when co-occurring with a disease-causing variant, and therefore understanding their modulating role in health and disease is of great importance. The polymorphic p.His558Arg variant of the sodium voltage-gated channel alpha subunit 5 (Na(V)1.5) encoded by the SCN5A gene is a case in point, as several studies have shown it can modify the clinical phenotype in a number of cardiac diseases. To evaluate the genetic backgrounds associated with this modulating effect, we reanalysed previous electrophysiological findings regarding the p.His558Arg variant and further assessed its patterns of genetic diversity in human populations. The Na(V)1.5 p.His558Arg variant was found to be in linkage disequilibrium with six other polymorphic variants that previously were also associated with cardiac traits in GWAS analyses. On account of this, incongruent reports that Arg558 allele can compensate, aggravate or have no effect on Na(V)1.5, likely might have arose due to a role of p.His558Arg depending on the additional linked variants. Altogether, these results indicate a major influence of the epistatic interactions between SCN5A variants, revealing also that phenotypic severity may depend on the polymorphic background associated to each individual genome.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 24