Failure to confirm association of a polymorphism in KCNMB4 gene with mesial temporal lobe epilepsy

Epilepsy Res. 2013 Sep;106(1-2):284-7. doi: 10.1016/j.eplepsyres.2013.03.014. Epub 2013 Apr 25.

Abstract

A recent study has implicated a tagging single nucleotide polymorphism (SNP) rs398702 located 3' of KCNMB4 (encoding calcium-activated potassium channel, subfamily M subunit beta 4) as a possible susceptibility allele for mesial temporal lobe epilepsy (mTLE). Such a finding warrants a further well-powered study in additional carefully phenotyped cohorts. Here we examined the role of the SNP (rs398702) in a cohort of 332 patients (182 women and 150 men; mean±SD age: 47.06±18.12) who had diagnoses of mTLE. None of the patients had a mass lesion, malformations of cortical development, or traumatic brain injury. Brain MRI study revealed hippocampal sclerosis (Hs) in 86/332 (26%) patients. Most patients (254/332, 76%) patients had drug-responsive mTLE. We also enrolled 335 healthy controls (164 women and 171 men; mean±SD age: 48.20±21.90), matched for age, sex and ethnicity. All patients and controls were Caucasian and were born in Italy. The genotype distribution of the SNP rs398702 in patients and controls was within Hardy-Weinberg equilibrium (p>0.05). There was no statistically significant difference in the genotype or allelic frequencies between patients and controls (p=0.878 and p=0.666 respectively). Moreover, such a variant did not influence the main clinical characteristics of mTLE, the presence of Hs or responsiveness to antiepileptic drugs. In conclusion, our data suggest that the rs398702 variant in the KCNMB4 gene is unlikely to influence significantly the risk of developing mTLE or its severity. They further highlight the importance of replication to confirm the validity of association study results.

Keywords: Association studies; Candidate gene; Genetic susceptibility; KCNMB4; Mesial temporal lobe epilepsy; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / therapeutic use
  • Brain / pathology
  • Cohort Studies
  • Electroencephalography
  • Epilepsy, Temporal Lobe / drug therapy
  • Epilepsy, Temporal Lobe / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Hippocampus / pathology
  • Humans
  • Italy / epidemiology
  • Large-Conductance Calcium-Activated Potassium Channel beta Subunits / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results
  • Sclerosis / pathology
  • White People

Substances

  • Anticonvulsants
  • KCNMB4 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel beta Subunits
  • Nerve Tissue Proteins