title: Gene-wide tagging study of the association between KCNT1 polymorphisms and the susceptibility and efficacy of genetic generalized epilepsy in Chinese population.
abstract: OBJECTIVE
  The causes of genetic generalized epilepsies (GGEs) are still uncertain now. Some studies found that the human potassium channel, subfamily T, member 1 (KCNT1) is the candidate gene causing malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy which are all rare genetic generalized epilepsies. The aims of this study were going to evaluate the association between KCNT1 common variations and the susceptibility and drug resistance of genetic generalized epilepsies in Chinese population.
  
  
  METHODS
  The allele-specific MALDI-TOF mass spectrometry method was used to assess 17 tagSNPs (tagged single-nucleotide polymorphisms) of KCNT1 in 284 healthy Chinese controls and 483 Chinese GGEs patients including 279 anti-epileptic drug-responsive patients and 204 drug-resistant patients.
  
  
  RESULTS
  Genotype distributions of all the selected tagSNPs were consistent with Hardy-Weinberg equilibrium in GGEs and healthy controls. None of the all 17 tagSNPs alleles were found to be related with the susceptibility and drug resistance of genetic generalized epilepsies. The frequencies of haplotype 5 and haplotype 1 were significantly lower in GGEs than that in healthy controls (2% vs. 4%, OR = 0.47 [0.27-0.94], P = 0.03) and obviously higher in drug-resistant patients than that in drug-response patients (6% vs. 3%, OR = 2.56 [1.23-5.35], P = 0.01). However, after the correction of multiple comparisons with Bonferroni's method, we found that the above two haplotypes were not associated with the susceptibility and drug resistance in GGEs and healthy controls.
  
  
  CONCLUSIONS
  This gene-wide tagging study revealed no association between KCNT1 17 common variations and susceptibility of GGEs or AEDs (anti-epileptic drugs) efficacy of genetic generalized epilepsies in Chinese population.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University Xiangya School of Medicine, Changsha, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Yang
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Mao
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Li
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Long
authors.forename: Nan
authors.initials: N
authors.lastname: Lv
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tang
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Hu
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002681:China / Q000453:epidemiology; D004351:Drug Resistance / Q000235:genetics; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015221:Potassium Channels / Q000235:genetics*; D000081033:Potassium Channels, Sodium-Activated; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; C585122:KCNT1 protein, human; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated
keywords: Drug resistance; Efficacy; Genetic generalized epilepsies; Genetic polymorphism; KCNT1; Susceptibility