ERCC6L2 rs591486 polymorphism and risk for amyotrophic lateral sclerosis in Greek population.
ALS
ERCC6L2
Oxidative stress
Pesticides
Polymorphism
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:
Jun 2019
Jun 2019
Historique:
received:
13
11
2018
accepted:
05
03
2019
pubmed:
18
3
2019
medline:
4
12
2019
entrez:
18
3
2019
Statut:
ppublish
Résumé
Α number of genetic variants have been associated with amyotrophic lateral sclerosis (ALS). A recent study supports that rs591486 across the ERCC6L2 gene and exposure to pesticides seem to have a joint effect on the development of Parkinson's disease, a disease which shares a few common characteristics with ALS. To detect a possible contribution of rs591486 ERCC6L2 to ALS. A total of 155 patients with ALS and 155 healthy controls were included in the study and genotyped for rs591486. Using logistic regression analyses (crude and adjusted for age and sex), rs591486 was tested for association with ALS risk. Subgroup analysis based on ALS site of onset was also performed. Cox regression analysis was applied in order for the effect of ERCC6L2 rs591486 on ALS age of onset to be tested. Adjusted analysis showed that ERCC6L2 rs591486 was associated with an increased risk of ALS development, in dominant [odds ratio, OR (95% confidence interval, CI) 2.15 (1.04-4.46), p = 0.037] and over-dominant [OR (95%CI) = 1.91 (1.01-3.60), p = 0.043], modes. Subgroup analysis based on ALS site of onset revealed an association between ERCC6L2 rs591486 and ALS with limb onset. Results for Cox regression analysis indicated that G/A carriers had a lower age of ALS limb onset when compared to G/G carriers. The current study provides preliminary indication for an implication of ERCC6L2 rs591486 in ALS development, as a possible genetic risk factor. These results possibly suggest that oxidative stress may be the main contributor in the pathophysiology of ALS.
Sections du résumé
BACKGROUND
BACKGROUND
Α number of genetic variants have been associated with amyotrophic lateral sclerosis (ALS). A recent study supports that rs591486 across the ERCC6L2 gene and exposure to pesticides seem to have a joint effect on the development of Parkinson's disease, a disease which shares a few common characteristics with ALS.
OBJECTIVE
OBJECTIVE
To detect a possible contribution of rs591486 ERCC6L2 to ALS.
METHODS
METHODS
A total of 155 patients with ALS and 155 healthy controls were included in the study and genotyped for rs591486. Using logistic regression analyses (crude and adjusted for age and sex), rs591486 was tested for association with ALS risk. Subgroup analysis based on ALS site of onset was also performed. Cox regression analysis was applied in order for the effect of ERCC6L2 rs591486 on ALS age of onset to be tested.
RESULTS
RESULTS
Adjusted analysis showed that ERCC6L2 rs591486 was associated with an increased risk of ALS development, in dominant [odds ratio, OR (95% confidence interval, CI) 2.15 (1.04-4.46), p = 0.037] and over-dominant [OR (95%CI) = 1.91 (1.01-3.60), p = 0.043], modes. Subgroup analysis based on ALS site of onset revealed an association between ERCC6L2 rs591486 and ALS with limb onset. Results for Cox regression analysis indicated that G/A carriers had a lower age of ALS limb onset when compared to G/G carriers.
CONCLUSIONS
CONCLUSIONS
The current study provides preliminary indication for an implication of ERCC6L2 rs591486 in ALS development, as a possible genetic risk factor. These results possibly suggest that oxidative stress may be the main contributor in the pathophysiology of ALS.
Identifiants
pubmed: 30879219
doi: 10.1007/s10072-019-03825-3
pii: 10.1007/s10072-019-03825-3
doi:
Substances chimiques
DNA Helicases
EC 3.6.4.-
ERCC6L2 protein, human
EC 3.6.4.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1237-1244Subventions
Organisme : The study was supported in part by a research grant of the Research Committee of the University of Thessaly, Greece (Code: 5287).
ID : 5287
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