title: Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies.
abstract: OBJECTIVE
  ATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population.
  
  
  METHODS
  Six ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI-TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls.
  
  
  RESULTS
  Significant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR)=0.807 (0.68-0.960), p=0.021 and 0.4% vs. 3.2%, OR=0.121 (0.026-0.565), p=0.002, respectively). The frequency of the rs8107107 CT+CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR=0.327 (0.248-0.942), p=0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance.
  
  
  CONCLUSIONS
  Our findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Chen-Xue
authors.initials: CX
authors.lastname: Mao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Mao
authors.affiliation: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410078, China.
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Long
authors.affiliation: Department of Neurology, Hunan Childrens Hospital, Changsha 410007, China.
authors.forename: Jia-E
authors.initials: JE
authors.lastname: Gong
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China. Electronic address: liuzhaoqian63@126.com.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D004829:Epilepsy, Generalized / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D055815:Young Adult
chemical_list: C488756:ATP1A3 protein, human; C498531:ATP1A2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
keywords: ATP1A2; ATP1A3; Anti-epileptic drugs; Genetic generalized epilepsies; Polymorphism