Efthimios Dardiotis1, Emmanouil Karampinis2, Vasileios Siokas2, Athina-Maria Aloizou2, Dimitrios Rikos2, Styliani Ralli2, Dimitra Papadimitriou3, Dimitrios P Bogdanos4,5, Georgios M Hadjigeorgiou6. 1. Department of Neurology, University Hospital of Larissa, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41100, Larissa, Greece. edar@med.uth.gr. 2. Department of Neurology, University Hospital of Larissa, Laboratory of Neurogenetics, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41100, Larissa, Greece. 3. Neurological Department, Henry Dunant Hospital Center, 107 Mesogeion Avenue, 11526, Athens, Greece. 4. Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, 40500, Larissa, Greece. 5. Cellular Immunotherapy & Molecular Immunodiagnostics, Biomedical Section, Centre for Research and Technology-Hellas (CERTH)- Institute for Research and Technology-Thessaly (IRETETH), 41222, Larissa, Greece. 6. Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
Abstract
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: To detect a possible contribution of rs591486 ERCC6L2 to ALS. 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: 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: 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.
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: To detect a possible contribution of rs591486ERCC6L2 to ALS. 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 ERCC6L2rs591486 on ALS age of onset to be tested. RESULTS: Adjusted analysis showed that ERCC6L2rs591486 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 ERCC6L2rs591486 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: The current study provides preliminary indication for an implication of ERCC6L2rs591486 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.