Variations in the TRPV1 gene are associated to exertional heat stroke.
J Sci Med Sport
; 23(11): 1021-1027, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-32471784
ABSTRACT
OBJECTIVES:
Exertional Heat Stroke (EHS) is one of the top three causes of sudden death in athletes. Extrinsic and intrinsic risk factors have been identified but the genetic causes still remain unclear. Our aim was to identify genes responsible for EHS, which is a necessary step to identify patients at risk and prevent crises.DESIGN:
Genetic and functional laboratory studiesMETHODS:
Whole Exome Sequencing (WES) was performed to search for candidate genes in a cohort of 15 soldiers who had a documented EHS episode. In silico and in vitro functional studies were performed to evaluate the effect of mutations identified in the candidate gene TRPV1.RESULTS:
WES led to the identification of two missense variations in the TRPV1 gene. These variations were very rare or unreported in control databases and located in critical domains of the protein. In vitro functional studies revealed that both variations induce a strong modification of the channel response to one of its natural agonist, the capsaicin.CONCLUSIONS:
We evidenced mutations altering channel properties of the TRPV1 gene and demonstrated that TRPV1, which is involved in thermoregulation and nociception, is a new candidate gene for EHS. Our data provide the bases to explore genetic causes and molecular mechanisms governing the pathophysiology of EHS.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Golpe de Calor
/
Predisposição Genética para Doença
/
Canais de Cátion TRPV
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Sci Med Sport
Assunto da revista:
MEDICINA ESPORTIVA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França