SLC2A3 rs12842 polymorphism and risk for Alzheimer’s disease

ABSTRACT

Background

Many studies support the hypothesis that brain glucose dysregulation contributes to neurodegeneration and disease progression. The SLC2A3 gene encodes the Neuronal Glucose Transporter 3 (GLUT3), a critical molecule for glucose transport into the neuron. The GLUT3 rs12842 polymorphism has been associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). Epidemiological and genetic studies have reported a link between antecedent ADHD and Alzheimer’s disease (AD), as both share a dysregulation of brain glucose.

Aim

This study aimed to explore the possible correlation of the SLC2A3 rs12842 polymorphism with susceptibility towards AD.

Methods

We genotyped 327 patients with AD and 327 controls for the GLUT3 rs12842. Results: Rs12842 was associated with a decreased risk of developing AD in the co-dominant [Odds Ratio (OR) (95% confidence interval (CI) = 0.67 (0.45–0.99)), p = 0.039], dominant [OR (95% CI) = 0.64 (0.44–0.93), p = 0.019] and log-additive modes [OR (95% CI) = 0.65 (0.46–0.91), p = 0.012].

Conclusions

Our results suggest a significant, inverse association between SLC2A3 rs12842 and the risk of AD.

KEYWORDS:

• AD
• genetics
• SLC2A3
• rs12842 SNPs
• polymorphism

Acknowledgements

Informed consent: ‘Informed consent was obtained from all individual participants included in the study.’

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

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

Notes on contributors

Stylianos Arseniou

Stylianos Arseniou is a neurologist with sub-specialisation in Clinical Neurophysiology. He is currently a PhD candidate of the University of Thessaly, Faculty of Medicine. He has several publications in the field of neurology and neuropsychiatry. He has several oral presentations and posters at national and international conferences on Neuropsychiatry and Neurodegenerative diseases. He holds a post as Clinical Fellow in the Department of clinical Neurophysiology, National Hospital of Neurology and Neurosurgery, UCLH, London, UK.

Vasileios Siokas

Vasileios Siokas (MD, MSc, PhD) is a resident in Neurology. He is a researcher in the Department of Neurology and Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, in Greece. His research focused in genetics of neurological diseases and meta-analyses of clinical and genetic studies.

Athina-Maria Aloizou

Athina-Maria Aloizou is a PhD Candidate in Neurology, at the University of Thessaly. She graduated the Medical School of Larissa, University of Thessaly, in 2019 and is currently also following a MSc course in Neurorehabilitation at the same Institution. She collaborates with the Neurology Department and the Laboratory of Neurogenetics of the University Hospital of Larissa, with published work on domains such as Multiple Sclerosis, Stroke, microRNAs, Neurotoxicology/Pesticides and Neurogenetics.

Polyxeni Stamati

Polyxeni Stamati is a neurologist and holds the post in the Neurology Department of the General Hospital Asklepeio Voulas in Athens, Greece for the last three years. She has recent publications in the field of neuroscience, and several presentations at national conferences on neurological disorders. She is also a PhD student of the Faculty of Medicine of the University of Thessaly.

Alexios-Fotios A. Mentis

Alexios-Fotios A. Mentisis a physician, public health scientist, and geneticist trained in Baltimore, US and Athens, Greece, and he is currently a PhD candidate supported through scholarship by the Alexander Onassis Foundation. His research interests in the field of neurology cover several areas, spanning from neuroepidemiology and meta-research to neurogenetics and neurogenomics.

Zisis Tsouris

Zisis Tsouris is medical doctor with a Masters’ in Clinical Applications of Molecular Medicine and holds a Diploma in Medicine (MD). He has several publications in the field of neuroscience. He has also oral presentations and numerous posters at national and international conferences on Neurological Disorders and Neurodegenerative diseases. He is currently a PhD student of the Faculty of Medicine of the University of Thessaly and holds a post as a resident in Neurology in the Department of Neurology, University Hospital of Larissa, Greece.

Metaxia Dastamani

Metaxia Dastamani is a doctor with a Diploma in Medicine (MD). She also holds a Degree in Biochemistry and Biotechnology with a Masters’ in «Biology of Reproduction». She has several publications in the field of neuroscience. She also has oral presentations and posters at national conferences. She is currently a Ph.D. student of the Department of Neurology, Faculty of Medicine of the University of Thessaly, and holds a Rural GP position in Thessaly, Central Greece. Concurrently, she actively participates in most of the proceedings of the Department of Neurology, University Hospital of Larissa, Greece.

Eleni Peristeri

Eleni Peristeri is a neurolinguist with a Master’s degree in Clinical Linguistics and a PhD in Neurolinguistics. She has several publications in the field of language and cognitive control processes in patients with post-stroke aphasia, normal ageing and neurodevelopmental disorders. She also has numerous oral presentations at renowned national and international conferences regarding neurodegenerative diseases, clinical aphasiology and bilingualism effects on the language and cognitive skills of individuals with language disorders. She’s been a lecturer under contract for six years at the Aristotle University of Thessaloniki, Greece, lecturing on models of language production and comprehension, first language acquisition and psycholinguistics, and she has recently earned a tenure track lecturer position at the Faculty of Medicine, University of Thessaly, Greece.

Varvara Valotassiou

Varvara Valotassiou received her BSc in Medicine from the Medical School of Aristotle University of Thessaloniki. She was specialized in Nuclear Medicine at the Nuclear Medicine Department of “Alexandra University Hospital” in Athens. She has worked at the Nuclear Medicine Department and PET/CT Department of Diagnostic and Therapeutic Center of Athens “HYGEIA”. Currently, she is working at the Department of Nuclear Medicine, University Hospital of Larissa, Greece. She obtained her Ph. D. degree from Faculty of Medicine, School of Health Sciences, University of Thessaly, Greece. Her research is focused on Nuclear Neurology, especially neuroimaging in dementia and movement disorders and has coauthored 53 publications including Neurology.

Dimitrios P. Bogdanos

Dimitrios P. Bogdanos is a Professor of Medicine and Autoimmune Diseases, and is the Director and Chairman of the Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece. He has been awarded an MD from the Aristotle University of Thessaloniki (1997) and a PhD from the University College London, University of London (2005). His research, focused on the role of molecular mimicry as a mechanism inducing autoimmunity, has been conducted at University College London (1998-2002), Yale School of Medicine (2001) and King’s College London (2003-2011). He has been the recipient of the Dame Sheila Sherlock Medal (2005) and awarded a CLS Award from the Higher Education Funding Council of England (HEFCE) in 2007. He has obtained a Professorship in Liver Immunopathology, Division of Transplantation Immunology and Mucosal Biology, King’s College London (2011). He has earned more than 35 prizes-awards for his scientific work on the diagnostic and clinical significance of disease-related autoantibodies, the role played microbial triggers of autoimmunity and the contribution of immunoregulation in autoimmune and inflammatory diseases. Professor Bogdanos was the first in his native country to obtain a Professorship at the post of Autoimmune Diseases. He is carrying experimental work and collaborative projects with academic institutions from all over the world funded by EU and prestigious grant giving bodies. He is participating in more than 25 multi-centre international clinical and research trials as principal or co-investigator. He is heading an active group of 15 post-doc, PhD, MSc students and technicians. He is an editor, associate editor or member of the editorial board in more than 20 journals. He has published more than 300 papers/chapters in books.

Georgios M. Hadjigeorgiou

Georgios Hadjigeorgiou has graduated from the School of Medicine of the National & Kapodistrian University of Athens where he also earned his Doctoral degree (both degrees with excellence). His postdoctoral training includes post-doctoral research fellowships at the University of Milano and at Columbia University, New York, in the field of genetics of metabolic myopathies and mitochondrial encephalomyopathies. He is currently a Professor of Neurology at the Medical Schools of the University of Cyprus and the University of Thessaly, Greece. His research focuses on the genetic epidemiology of movement disorders, neurodegenerative diseases and other neurological disorders, including stroke, multiple sclerosis, Restless Legs Syndrome, etc. His research group is an active member of the genetic epidemiology consortium of Parkinson’s disease (GEO-PD), International Multiple Sclerosis Genomics Consortium (IMSGC) and the European Restless Legs Study Group (EURLSSG). He is reviewer in more than 40 international scientific journals and he has been the Principal Investigator of more than 20 national and international collaborative research projects. His research output includes more than 280 PubMed publications with a Scopus h-index= 42 and more than 7000 citations.

Efthimios Dardiotis

Efthimios Dardiotis is an Assοciate Professor of Neurology at the Department of Neurology and Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Greece. He has graduated from the Faculty of Medicine of the Aristotle University of Thessaloniki, while he earned his PhD thesis at the Department of Neurology of the University of Thessaly, Greece. His research interests focus on the genetic epidemiology of Multiple Sclerosis, Amyatrophic Lateral Sclerosis, Guillain-Barré Syndrome, Alzheimer’s disease and Parkinson’s disease, while his research also includes the genetic basis and epidemiology of myopathies. He is a member of various international scientific committees, such as the European Neurological Society and the European Federation of Neurological Societies, and a reviewer in more than 20 international scientific journals. His research output includes more than 200 PubMed publications with a Scopus h-index= 30 and more than 3500 citations.