CYP1A2 rs762551 polymorphism and risk for amyotrophic lateral sclerosis.
ALS
CYP1A2
Oxidative stress
Polymorphism
rs762551
Journal
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
20
02
2020
accepted:
21
06
2020
pubmed:
28
6
2020
medline:
15
5
2021
entrez:
28
6
2020
Statut:
ppublish
Résumé
Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated. This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme. One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats. The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS. Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.
Sections du résumé
BACKGROUND
BACKGROUND
Genetic variability is considered to confer susceptibility to amyotrophic lateral sclerosis (ALS). Oxidative stress is a significant contributor to ALS-related neurodegeneration, and it is regulated by cytochromes P450 (CYPs), such as CYP1A2; these are responsible for the oxidative metabolism of both exogenous and endogenous substrates in the brain, subsequently impacting ALS. The function of CYP1A2 is largely affected by genetic variability; however, the impact of CYP1A2 polymorphisms in ALS remains underinvestigated.
OBJECTIVE
OBJECTIVE
This study aims to examine the possible association of ALS with the CYP1A2 rs762551 polymorphism, which codes for the high inducibility form of the enzyme.
METHODS
METHODS
One hundred and fifty-five patients with sporadic ALS and 155 healthy controls were genotyped for the CYP1A2 rs762551. Statistical testing for the association of CYP1A2 rs762551 with risk for ALS was performed using SNPstats.
RESULTS
RESULTS
The CYP1A2 rs762551 C allele was associated with a decreased risk of ALS development. In the subgroup analysis according to the ALS site of onset, an association between CYP1A2 rs762551 and limb and bulbar onset of ALS was shown. Cox proportional-hazard regression analyses revealed a significant effect of the CYP1A2 rs762551 on the age of onset of ALS.
CONCLUSIONS
CONCLUSIONS
Based on our results, a primarily potential link between the CYP1A2 rs762551 polymorphism and ALS risk could exist.
Identifiants
pubmed: 32592103
doi: 10.1007/s10072-020-04535-x
pii: 10.1007/s10072-020-04535-x
doi:
Substances chimiques
CYP1A2 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1A2
EC 1.14.14.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
175-182Subventions
Organisme : The study was supported in part by a research grant of the Research Committee of the University of Thessaly, Greece (Code: 5287).
ID : Code: 5287
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