title: Xenobiotic metabolizing and transporter genes: gene-gene interactions in schizophrenia and related disorders.
abstract: OBJECTIVE
  In this study we explored possible epistasis between CYP2D6 (*3, *4, *5, *6 and *1xN), CYP3A5 (*3), CYP1A2 (*1C and *1F) and ABCB1 (G2677T) in schizophrenia and related disorders.
  
  
  METHODS
  A total of 344 patients diagnosed with schizophrenia and related disorders, and 484 healthy controls participated in the present study. We analyzed gene-gene interactions by multifactor dimensionality reduction.
  
  
  RESULTS
  A four-way model including ABCB1 G2677T, CYP3A5*3, CYP1A2*1F and CYP2D6*4 variants had the best overall performances (accuracy: 0.573) and a crossvalidation consistency of 10/10 (permutation testing p < 0.004).
  
  
  CONCLUSIONS
  Our results suggest a significant involvement of CYPs and transporters in brain metabolism and homeostasis, and provide evidence of gene-gene interactions among xenobiotic metabolizing and transporter genes in the context of schizophrenia.
authors.affiliation: Department of Anatomic Pathology, University of Barcelona, Casanova 143, E-08036, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Santi
authors.initials: S
authors.lastname: Alvarez
authors.forename: Gemma
authors.initials: G
authors.lastname: Trias
authors.forename: Miquel
authors.initials: M
authors.lastname: Bioque
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliveira
authors.forename: Miquel
authors.initials: M
authors.lastname: Bernardo
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D001692:Biological Transport / Q000235:genetics; D001921:Brain / Q000201:enzymology; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D003627:Data Interpretation, Statistical; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000201:enzymology / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics; D012563:Schizophrenia, Paranoid / Q000201:enzymology / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015262:Xenobiotics; C504573:CYP1A2 protein, human; C510164:CYP3A5 protein, human; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A