NeuroMolecular Medicine

, Volume 21, Issue 1, pp 68–74 | Cite as

BDNF rs6265 (Val66Met) Polymorphism as a Risk Factor for Blepharospasm

  • Vasileios Siokas
  • Dimitrios Kardaras
  • Athina-Maria Aloizou
  • Ioannis Asproudis
  • Konstadinos G. Boboridis
  • Eleni Papageorgiou
  • Georgios M. Hadjigeorgiou
  • Evangelia E. Tsironi
  • Efthimios DardiotisEmail author
Original Paper


A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. The effect of rs6265 on BSP was evaluated. 206 patients with BSP and 206 healthy controls were recruited and genotyped for the rs6265. We also performed a meta-analysis, by pooling our results with those from previous studies. A significant effect of rs6265 on the risk of BSP was found in the dominant model of inheritance [odds ratio (OR) (95% confidence interval (CI) 1.52 (1.01–2.29), p = 0.044]. Mutational load analysis of rs6265 in the risk of BSP using the ORG revealed that higher load of the “A” allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.48; 95% CI 1.00–2.19). Finally, pooled results from the meta-analysis revealed that the rs6265 is associated with an increased risk of BSP in the dominant model [OR 1.26; 95% CI 1.02–1.55, pz = 0.03]. Also, higher load of the “A” allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.26; 95% CI 1.04–1.53). The present study provides additional evidence to the existing knowledge concerning the contribution of the rs6265 BDNF on the risk of developing BSP. While the pathophysiology and genetic susceptibility in BSP and focal dystonia are only partially understood, it seems that BDNF and rs6265 may constitute one essential risk factor that is heavily involved.


BDNF Blepharospasm Focal dystonia Polymorphism SNP 


Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

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

Supplementary material

12017_2018_8519_MOESM1_ESM.docx (14 kb)
Supplementary File 1 The complete search algorithm. (DOCX 13 KB)
12017_2018_8519_MOESM2_ESM.doc (31 kb)
Supplementary File 2 Flow chart presenting the selection of eligible studies. (DOC 31 KB)
12017_2018_8519_MOESM3_ESM.doc (63 kb)
Supplementary File 3 PRISMA 2009 Checklist. (DOC 63 KB)
12017_2018_8519_MOESM4_ESM.docx (21 kb)
Supplementary Table 1—Characteristics of the studies included in the meta-analysis. Supplementary Table 2—Quantitate measures of genetic risk (individual study estimates and pooled effects), for the rs6265 and the BSP risk, with the generalized odds ratio (ORG). (DOCX 20 KB)
12017_2018_8519_MOESM5_ESM.tif (55 kb)
Supplementary Figure 1 Funnel plots assessing evidence of publication bias in overall studies for BDNF rs6265 included in meta-analysis for BSP group. SE, standard error; OR, odds ratio. (TIF 55 KB)
12017_2018_8519_MOESM6_ESM.tif (205 kb)
Supplementary Figure 2 Funnel plots assessing evidence of publication bias in studies with Caucausian/European cohorts for BDNF rs6265 included in meta-analysis for BSP group. SE, standard error; OR, odds ratio (TIF 205 KB)
12017_2018_8519_MOESM7_ESM.tif (339 kb)
Supplementary Figure 3 Forest plots assessing odds ratios of BSP associated with rs6265 BDNF polymorphism in overall studies included in meta-analysis (TIF 338 KB)
12017_2018_8519_MOESM8_ESM.tif (320 kb)
Supplementary Figure 4 Forest plots assessing odds ratios of BSP associated with rs6265 BDNF polymorphism in studies with Caucasian/European Cohorts included in meta-analysis. (TIF 320 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vasileios Siokas
    • 1
  • Dimitrios Kardaras
    • 2
  • Athina-Maria Aloizou
    • 1
  • Ioannis Asproudis
    • 3
  • Konstadinos G. Boboridis
    • 4
  • Eleni Papageorgiou
    • 2
  • Georgios M. Hadjigeorgiou
    • 1
    • 5
  • Evangelia E. Tsironi
    • 2
  • Efthimios Dardiotis
    • 1
    Email author
  1. 1.Laboratory of Neurogenetics, Department of Neurology, University Hospital of LarissaUniversity of ThessalyLarissaGreece
  2. 2.Department of Ophthalmology, University Hospital of LarissaUniversity of ThessalyLarissaGreece
  3. 3.Department of OphthalmologyUniversity of IoanninaIoanninaGreece
  4. 4.3rd University Department of OphthalmologyAristotle University of ThessalonikiThessalonikiGreece
  5. 5.Department of Neurology, Medical SchoolUniversity of CyprusNicosiaCyprus

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