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ERCC6L2 rs591486 polymorphism and risk for amyotrophic lateral sclerosis in Greek population

  • Efthimios DardiotisEmail author
  • Emmanouil Karampinis
  • Vasileios Siokas
  • Athina-Maria Aloizou
  • Dimitrios Rikos
  • Styliani Ralli
  • Dimitra Papadimitriou
  • Dimitrios P. Bogdanos
  • Georgios M. Hadjigeorgiou
Original Article

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.

Keywords

ALS Oxidative stress Pesticides Polymorphism ERCC6L2 

Notes

Funding

The study was supported in part by a research grant of the Research Committee of the University of Thessaly, Greece (Code: 5287).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Supplementary material

10072_2019_3825_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 15 kb)

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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  • Efthimios Dardiotis
    • 1
    Email author
  • Emmanouil Karampinis
    • 1
  • Vasileios Siokas
    • 1
  • Athina-Maria Aloizou
    • 1
  • Dimitrios Rikos
    • 1
  • Styliani Ralli
    • 1
  • Dimitra Papadimitriou
    • 2
  • Dimitrios P. Bogdanos
    • 3
    • 4
  • Georgios M. Hadjigeorgiou
    • 5
  1. 1.Department of Neurology, University Hospital of Larissa, Laboratory of Neurogenetics, Faculty of MedicineUniversity of ThessalyLarissaGreece
  2. 2.Neurological DepartmentHenry Dunant Hospital CenterAthensGreece
  3. 3.Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health SciencesUniversity of ThessalyLarissaGreece
  4. 4.Cellular Immunotherapy & Molecular Immunodiagnostics, Biomedical SectionCentre for Research and Technology-Hellas (CERTH)- Institute for Research and Technology-Thessaly (IRETETH)LarissaGreece
  5. 5.Department of Neurology, Medical SchoolUniversity of CyprusNicosiaCyprus

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