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ABSTRACT
Background: Migraine is a complex multifactorial disorder and its pathogenesis still remains unclear. Evidence suggests the involvement of the activated trigeminovascular pathway, in which BDNF seems to play an important role. Therefore, BDNF polymorphisms are promising candidate susceptibility factors.
Aim: BDNF rs6265 functional polymorphism was analyzed in order to determine its possible association with pediatric headache and migraine risk.
Methods: The research included 120 consecutive pediatric patients who were diagnosed with headache and 120 healthy controls. The diagnosis was in compliance with the International Classification of Headache Disorders. Blood samples were collected from all participants and genotyped for rs6265.
Results: BDNF rs6265 was significantly associated with decreased headache risk, particularly in the dominant model [Odds Ratio, OR (95% confidence interval, C.I.): 0.47 (0.26–0.85), p = 0.011] and the log-additive model [OR (95% C.I.): 0.48 (0.28–0.82), p = 0.0053]. During the sensitivity analysis, the associations were also maintained among patients with migraine.
Conclusions: This is the first study to reveal a significant association of this BDNF variant with headache risk. Additionally, Val66Met was also for the first time related to decreased childhood migraine risk.
Disclosure statement
No potential conflict of interest was reported by the authors.
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.’
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Funding
Notes on contributors
Vasiliki Koute
Vasiliki Koute I received the Medical Degree in Aristotle University of Thessaloniki on 1988 and the Specialty of Pediatrics, in Thessaloniki, on beginning of 1996.In the meanwhile I served for almost two years in Primary Healthcare service. I was educated in Pediatric Neurology, as S.H.O firstly, and Registrar, later, in University Hospitals of Manchester, Royal Manchester and Booth Hall Children Hospitals, United Kingdom, coming back in Greece, end of 1996. Between 1997-17/1/2002 I asked private Medicine in Pediatrics and Pediatric Neurology, serving as well as in the most important Health National Insurance Company, in Greece, as Consultant Pediatrician, for three and a half years, in Larissa. Since 17/1/2002, till now, I serve as Registrar in Pediatric Neurology, firstly for 8 years, Senior Registrar for next 7 years and as Consultant Pediatric Neurologist for the last almost 5 and a half years, in University Hospital of Larissa, Pediatric Department, University of Thessaly, dealing with the investigation and treatment of Pediatric Neurology patients in Central Greece area. I still work on research for my Ph.D., dealing with genetics and headache in children of Central Greece.
Amalia Michalopoulou
Prof. Georgios Hadjigeorgiou is a Professor/Chair of the Department of Neurology and Associate Dean, Medical School, University of Cyprus. He received his MD and PhD degree from Kapodistrian & National University of Cyprus. Previous academic positions include Professor of Neurology/Chair of the Department of Neurology and Dean of the Faculty of Medicine, University of Thessaly, Greece. His postdoctoral training includes post-doctoral research fellowships at University of Milano, and Columbia University, New York. His major research interests include the field of the genetic epidemiology of complex neurological diseases
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 has been a PhD Candidate of the Neurology Department of the University of Thessaly since 2020. She graduated from the School of Medicine of the University of Thessaly in 2019, and is also attending the MSc of Neurorehabilitation of the same department. She has collaborated in various research projects with the Neurology Department since 2018, in the fields of Clinical Neurology, Neurotoxicology, Neuroimmunology, and Neurogenetics.
Dimitrios Rikos
Dimitrios Rikos received the medical degree from the Aristotle University of Thessaloniki in 2006 and at the same time graduated from the Military Corps Officers School. He works as a flight surgeon at the Hellenic Air Force since 2007. He received the Master of Science degree in Research Methodology, Biostatistics and Bioinformatics from the University of Thessaly in 2015 and in 2016 named as a Ph.D. candidate. His thesis deals with Parkinson disease genetics. He is a board-certified Neurologist since 2019. Since 2016 he has been engaged in the research of various neurologic topics (neurogenetics, multiple sclerosis, biomarkers) as member of a research group within the University of Thessaly/Faculty of Medicine and relevant teaching activities. Since 2019 he works as an associate treating physician at the migraine/interventional neurology special outpatient clinic of the University Hospital of Larissa, Greece.
Dimitrios P. Bogdanos
Alexandros Papadimitriou is Emeritus Professor of Neurology of the University of Thessaly in Greece. His research interests focus on the genetic epidemiology and the genetic basis of several neurological disorders. He is a member of various international scientifc committees and a reviewer in more than 20 international scientifc journals.
Eleftherios Kontopoulos
Eleftherios Kontopoulos. Pediatrician(1977). Phd Faculty of Medicin Aristotle University of Thessaloniki (AUTH)1980 Spec.in Pediatric Neurology(2nd neurol.DeptAUTH,and Royal Hosp.for Sick Children,Edinburgh) memberof staff of 1st Ped.Dept.AUTH since 1977. Assist.prof.,Assoc.Prof.,and Prof in Ped.Neurolody till 2011. Emeritus prof.since then.
Ioanna N. Grivea received M.D. degree in 1992 from Medical School of University of Athens. From 1995 to 1999 she was trained in pediatrics in School of Medicine, University of Patras. In Feb. 2001 she received her PhD degree from University of Patras. From 2002 to 2005 she served as assistant attending in the Department of Pediatrics, in the University Hospital of Patras. Subsequently, she entered academics in School of Medicine, University of Thessaly, as a Lecturer of Pediatrics (2006 -2010), as Assistant Professor of Pediatrics (2010-2016), as Associate Professor of Pediatrics and Neonatology (2016 through present). She has been engaged in the research of various pediatrics diseases and neonatology.
Ioanna N. Grivea
George A. Syrogiannopoulos has been Professor of Pediatrics at the University of Thessaly since 19/2/2004 and Director of the Pediatric Clinic & Neonatology Clinic – NICU of the University of Thessaly. He graduated from the Medical School of the University of Athens in 1978 and completed his residency in Pediatrics at the Pediatrics Clinic of the University of Patras. From 1984 to 1986 he trained in Pediatric Infections at the University of Texas Health Science Center in Dallas, Southwestern Medical School, Dallas, Texas, USA. From 1981 to 2004 he was a member of the academic community of the Medical School of the University of Patras and in 2003 he was elected Professor of Pediatrics - Pediatric Infections. His clinical work concerns the fields of general pediatrics and infections. His main interests in research are infections of the respiratory, musculoskeletal and central nervous systems.
Amalia Michalopoulou received her medical degree in July 2014. In 2015, she participated as an interviewer and examiner at the HELIAD study, an investigation about the impact of mediterranean nutrition and cognitive dysfunction. She obtained her MSc degree in Molecular Medicine in October 2016. Since 2017, she has been worked as a neurology resident at Chania General Hospital and General Hospital of Nikaia.
George A. Syrogiannopoulos
Alexandros Papadimitriou is Emeritus Professor of Neurology of the University of Thessaly in Greece. His research interests focus on the genetic epidemiology and the genetic basis of several neurological disorders. He is a member of various international scientifc committees and a reviewer in more than 20 international scientifc journals.
Alexandros Papadimitriou
Vasiliki Koute I received the Medical Degree in Aristotle University of Thessaloniki on 1988 and the Specialty of Pediatrics, in Thessaloniki, on beginning of 1996.In the meanwhile I served for almost two years in Primary Healthcare service. I was educated in Pediatric Neurology, as S.H.O firstly, and Registrar, later, in University Hospitals of Manchester, Royal Manchester and Booth Hall Children Hospitals, United Kingdom, coming back in Greece, end of 1996. Between 1997-17/1/2002 I asked private Medicine in Pediatrics and Pediatric Neurology, serving as well as in the most important Health National Insurance Company, in Greece, as Consultant Pediatrician, for three and a half years, in Larissa. Since 17/1/2002, till now, I serve as Registrar in Pediatric Neurology, firstly for 8 years, Senior Registrar for next 7 years and as Consultant Pediatric Neurologist for the last almost 5 and a half years, in University Hospital of Larissa, Pediatric Department, University of Thessaly, dealing with the investigation and treatment of Pediatric Neurology patients in Central Greece area. I still work on research for my Ph.D., dealing with genetics and headache in children of Central Greece.
Georgios M. Hadjigeorgiou
Prof. Georgios Hadjigeorgiou is a Professor/Chair of the Department of Neurology and Associate Dean, Medical School, University of Cyprus. He received his MD and PhD degree from Kapodistrian & National University of Cyprus. Previous academic positions include Professor of Neurology/Chair of the Department of Neurology and Dean of the Faculty of Medicine, University of Thessaly, Greece. His postdoctoral training includes post-doctoral research fellowships at University of Milano, and Columbia University, New York. His major research interests include the field of the genetic epidemiology of complex neurological diseases
Efthimios Dardiotis
Dimitrios P. Bogdanosis a Professor of Medicine and Autoimmune Diseases, Faculty of Medicine, School of Health Sciences. Larissa, Greece. He is also the Director of the Department of Rheumatology, and Clinical Immunology, University General Hospital of Larissa and the Vice Chairman of the Scientific Council of the Hospital. He has been awarded an MD from the Aristotle University of Thessaloniki, and a PhD from the University College London, University of London. Prof Bogdanos research has been focused on the role of molecular mimicry as a mechanism inducing autoimmunity and studied this at University College London, Yale School of Medicine and King’s College London from 1998-2011. He is the recipient of the Dame Sheila Sherlock Award from the British Association for the Study of the Liver (BASL) (2004). For his translational clinical research and has been awarded a CLS Award from the Higher Education Funding Council of England (HEFCE) in 2007. He has obtained a Professorship in Immunopathology (Hon), Division of Transplantation Immunology and Mucosal Biology, King’s College London (2011). He has earned more than 40 prizes, awards and distinctions for his scientific work on the diagnostic and clinical significance of disease-related autoantibodies and the role played by microbial triggers of autoimmunity. Professor Bogdanos was the first in his native country to obtain an academic position at the post of Autoimmune Diseases. He is a member of the World Academy of sciences. He is the Co-President of the Institute of Rheumatic and Autoimmune Diseases, an Institute that organizes the largest polythematic Congress on Autoimmune Diseases in Greece. Prof Bogdanos is carrying experimental work and collaborative projects with academic institutions from all over the world funded by various agencies and grant giving bodies. He is participating in multi centre international clinical 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 15 journals. He has published more than 400 papers/chapters in books (h-index: 57, citations: 10,260).
Efthimios Dardiotisis 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 scientifc committees, such as the European Neurological Society and the European Federation of Neurological Societies, and a reviewer in more than 20 international scientifc journals. His research output includes more than 200 PubMed publications with a Scopus h-index= 30 and more than 3500 citations.