title: Evidence of epistasis between the catechol-O-methyltransferase and aldehyde dehydrogenase 3B1 genes in paranoid schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a common yet severe psychiatric condition characterized by complex genetic mechanism and diverse clinical presentations. Our previous study indicated that the combined effect of two intronic single nucleotide polymorphisms (SNPs), which are located in the catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 3B1 (ALDH3B1) genes, respectively, conferred genetic risk to paranoid schizophrenia.
  
  
  METHODS
  To further explore the precise mechanism of the COMT and ALDH3B1 interaction involved in the pathophysiology of schizophrenia, we scanned all possible functional SNPs within these two genes by polymerase chain reaction (PCR)-based genotyping analysis in 540 paranoid schizophrenic patients and 660 control subjects from a Han Chinese population. We also determined the effects of schizophrenia-associated SNPs on the development of psychotic symptoms, P300 event-related potential components induced by an auditory odd-ball task, and gene expression examined by quantitative real-time PCR analysis.
  
  
  RESULTS
  The major findings of this study were that, among the individuals carrying the rs3751082 A allele in the ALDH3B1 gene, the rs4633 T allele in the COMT gene was associated with susceptibility to paranoid schizophrenia (p = .004), development of hallucination (p = 5.141 E-5), delay of P300 latency in both patients (p = .006) and control subjects (p = .02), and increased expression of the COMT gene in control subjects (p = .002). However, the rs4633 T allele did not show any association in the rs3751082 G/G genotype carriers.
  
  
  CONCLUSIONS
  These findings provided convincing evidence that epistasis between the COMT and ALDH3B1 genes plays an important role in the pathogenesis of schizophrenia.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science and Peking Union Medical College, Tsinghua University, Beijing, 100005, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.forename: Kerang
authors.initials: K
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Jintang
authors.initials: J
authors.lastname: Ma
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D004843:Epistasis, Genetic; D018913:Event-Related Potentials, P300 / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012563:Schizophrenia, Paranoid / Q000201:enzymology* / Q000235:genetics*
chemical_list: D012313:RNA; D000444:Aldehyde Dehydrogenase; D002394:Catechol O-Methyltransferase