Clinical Implication of Smoking-Related Aryl-Hydrocarbon Receptor Repressor (AHRR) Hypomethylation in Japanese Adults.
Circ J
; 86(6): 986-992, 2022 05 25.
Article
em En
| MEDLINE
| ID: mdl-35110429
ABSTRACT
BACKGROUND:
Tobacco smoking is a leading preventable cause of morbidity and mortality worldwide; still, the success rate of smoking cessation is low in general. From the viewpoint of public health and clinical care, an objective biomarker of long-term smoking behavior is sought.MethodsâandâResults:
This study assessed DNA methylation as a biomarker of smoking in a hospital setting through a combination of molecular approaches including genetic, DNA methylation and mRNA expression analyses. First, in an epigenome-wide association study involving Japanese individuals with chronic cardiovascular disease (n=94), genome-wide significant smoking association was identified at 2 CpG sites on chromosome 5, with the strongest signal at cg05575921 located in intron 3 of the aryl-hydrocarbon receptor repressor (AHRR) gene. Highly significant (P<1×10-27) smoking-cg05575921 association was validated in 2 additional panels (n=339 and n=300). For the relationship of cg05575921 methylation extent with time after smoking cessation and cumulative cigarette consumption among former smokers, smoking-related hypomethylation was found to remain for ≥20 years after smoking cessation and to be affected by multiple factors, such as cis-interaction of genetic variation. There was a significant inverse correlation (P=0.0005) between cg05575921 methylation extent and AHRR mRNA expression.CONCLUSIONS:
The present study results support that reversion of AHRR hypomethylation can be a quantifiable biomarker for progress in and observance of smoking cessation, although some methodological points need to be considered.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article