title: The roles of variants in human multidrug resistance (MDR1) gene and their haplotypes on antiepileptic drugs response: a meta-analysis of 57 studies.
abstract: OBJECTIVE
  Previous studies reported the associations between the ATP-binding cassette sub-family B member 1 (ABCB1, also known as MDR1) polymorphisms and their haplotypes with risk of response to antiepileptic drugs in epilepsy, however, the results were inconclusive.
  
  
  METHODS
  The Pubmed, Embase, Web of Science, CNKI and Chinese Biomedicine databases were searched up to July 15, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model based on heterogeneity tests. Meta-regression and Galbraith plot analysis were carried out to explore the possible heterogeneity.
  
  
  RESULTS
  A total of 57 studies involving 12407 patients (6083 drug-resistant and 6324 drug-responsive patients with epilepsy) were included in the pooled-analysis. For all three polymorphisms (C3435T, G2677T/A, and C1236T), we observed a wide spectrum of minor allele frequencies across different ethnicities. A significantly decreased risk of AEDs resistance was observed in Caucasian patients with T allele of C3435T variant, which was still significant after adjusted by multiple testing corrections (T vs C: OR=0.83, 95%CI=0.71-0.96, p=0.01). However, no significant association was observed between the other two variants and AEDs resistance. Of their haplotypes in ABCB1 gene (all studies were in Indians and Asians), no significant association was observed with AEDs resistance. Moreover, sensitivity and Cumulative analysis showed that the results of this meta-analysis were stable.
  
  
  CONCLUSIONS
  In summary, this meta-analysis demonstrated that effect of C3435T variant on risk of AEDs resistance was ethnicity-dependent, which was significant in Caucasians. Additionally, further studies in different ethnic groups are warranted to clarify possible roles of haplotypes in ABCB1 gene in AEDs resistance, especially in Caucasians.
authors: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
authors: Hui
authors: H
authors: Li
authors: Department of neurology, Huai'an Hospital of Traditional Chinese Medicine, Jiangsu, China.
authors: Bing
authors: B
authors: Wang
authors: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
authors: Cheng
authors: C
authors: Chang
authors: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
authors: Minghua
authors: M
authors: Wu
authors: Department of neurology, Nanjing Drum Tower Hospital affiliated with Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: Yun
authors: Y
authors: Xu
authors: Department of neurology, Jiangsu Province Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, China.
authors: Yajun
authors: Y
authors: Jiang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D004827:Epilepsy / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000927:Anticonvulsants