title: Association of insulin receptor H1085H C>T, insulin receptor substrate 1 G972R and insulin receptor substrate 2 1057G/A polymorphisms with refractory temporal lobe epilepsy in Han Chinese.
abstract: OBJECTIVE
  Insulin/insulin receptor (INSR) signaling plays diverse roles in the central nervous system, including regulation of blood glucose, synaptic plasticity, dendritic growth, modulation of electrophysiological activity, proliferation of astrocytes and neuronal apoptosis. Interestingly, many of these and/or related processes represent biological mechanisms associated with temporal lobe epilepsy (TLE). Thus, insulin signaling may play a role in the development of TLE and its therapeutic responses. We hypothesized that functional polymorphisms in the insulin pathway genes INSR, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with the therapeutic responses of TLE. Therefore, in this study we analyzed the association of three single nucleotide polymorphisms (SNPs) showing a risk for TLE drug resistance using a hospital-based case-control design.
  
  
  METHODS
  Two hundred and one patients with refractory TLE and one hundred and seventy-five drug-responsive TLE patients were recruited for the study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the genotypes of INSR His1085His, IRS1 G972R and IRS2 1057G/A.
  
  
  RESULTS
  No significant differences between refractory and drug-responsive TLE patients were observed for the IRS1 G972R and IRS2 1057G/A polymorphisms (P>0.05), but a significant association was found for the INSR His1085His polymorphism for both genotypes (P=0.035) and alleles (P=0.011). IRS2 1057G/A combined with the INSR His 1085 His polymorphism increased the odds ratio of drug resistance in TLE (P=0.011, OR=2.263, 95% CI: 1.208-4.239).
  
  
  CONCLUSIONS
  These results suggest that a genetic variation in the insulin signaling pathway genes may affect the therapeutic response of TLE.
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China; Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Che
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China. Electronic address: fuqingxi@aliyun.com.
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Linyi Health School, Linyi, Shandong 276003, PR China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Naiyong
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Faying
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China. Electronic address: feeling202@126.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D004351:Drug Resistance / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D000927:Anticonvulsants; D015703:Antigens, CD; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; C435941:INSR protein, human; D011972:Receptor, Insulin
keywords: Drug resistance; Epilepsy, temporal lobe; Insulin receptor substrate proteins; Polymorphism, single nucleotide