COQ2 and SNCA polymorphisms interact with environmental factors to modulate the risk of multiple system atrophy and subtype disposition.
Eur J Neurol
; 29(10): 2956-2966, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35748722
ABSTRACT
BACKGROUND AND PURPOSE:
Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C.METHODS:
A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model.RESULTS:
A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G-E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p < 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671-0.847). Modulated risk of MSA-C, with MSA-P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p < 0.05), with an AUC of 0.749 (95% CI = 0.683-0.815).CONCLUSIONS:
Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G-E interactions and MSA etiopathogenesis warrant further investigation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Praguicidas
/
Atrofia de Múltiplos Sistemas
/
Alquil e Aril Transferases
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Eur J Neurol
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Taiwan