Methylation of cation–chloride cotransporters NKCC1 and KCC2 in patients with juvenile myoclonic epilepsy

  • Fatma GençEmail author
  • Murat Kara
  • Yasemin Ünal
  • Elif Uygur Küçükseymen
  • Yasemin Biçer Gömceli
  • Taner Kaynar
  • Kürşad Tosun
  • Gülnihal Kutlu
Original Article


The etiology of juvenile myoclonic epilepsy (JME) is still unknown and the process of elaboration of multiple genetic mechanisms is ongoing. The aim of this study was to investigate the potential role of NKCC1 (SCL12A2) and KCC2 (SCL12A5) in JME by comparing their DNA methylation status in patients with JME versus healthy controls. Forty-nine patients with JME and 39 healthy individuals were compared for DNA methylation at the 5CpG islands. A total of 71 (81%) samples were found to have methylation in the NKCC1 gene, 36 (73%) from patients and 35 (90%) from healthy individuals. Out of the KCC2 samples, 50 (57%) were found to have methylation, 33 (67%) from patients and 17 (44%) from healthy individuals. In patients with JME, methylation of NKCC1 (73%) was lower than its methylation in the controls (90%) (p = 0.047). On the other hand, methylation of KCC2 in patients with JME (67%) was greater than the methylation in the controls (44%) (p = 0.022). Twenty-eight patients were treated with VPA and ongoing medications were not found to be associated with methylation (p > 0.05). In the present study, we determined significantly lower NKCC1 DNA methylation and significantly higher KCC2 DNA methylation levels in patients with JME compared with the healthy controls. This implies that NKCC1 expression can be higher and KCC2 expression can be reduced in affected people. Further studies that investigate the potential effect of DNA methylation mechanisms regulating gene expression on seizure activity and how they change JME network activity will be helpful.


Juvenile myoclonic epilepsy Epigenetic DNA methylation Cation–chloride cotransporters NKCC1 (SCL12A2), KCC2 (SCL12A5) 


Compliance with ethical standards

The study was approved by the Ethics Committee of Antalya Education and Research Hospital.

Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Antalya Training and Research Hospital, Department of NeurologyAntalyaTurkey
  2. 2.IstanbulTurkey
  3. 3.Faculty of Medicine Department of NeurologyMuğla Sıtkı Koçman UniversityMuğlaTurkey
  4. 4.Neuromodulation Center, Spaulding Rehabilitation HospitalHarvard Medical SchoolBostonUSA
  5. 5.Sitogen Biomedical and Laboratory Systems Industrial Trade Limited CompanyİstanbulTurkey
  6. 6.Siena CollegeLoudonvilleUSA
  7. 7.Faculty of Medicine Department of Neurology and Clinical NeurophysiologyMuğla Sıtkı Koçman UniversityMuğlaTurkey

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