title: Interactive effect of MTHFR and ADRA2A gene polymorphisms on pathogenesis of schizophrenia.
abstract: OBJECTIVE
  Increasing evidences support the importance of epigenetic control in schizophrenia pathogenesis. One of the enzymes involved in DNA methylation process through homocysteine metabolism is methylenetetrahydrofolate reductase (MTHFR). The most extensively studied variant in the MTHFR gene is the C677T polymorphism, resulting in reduced enzyme activity and elevated homocysteine level.
  
  
  METHODS
  In sample of 192 schizophrenics and 213 healthy controls an increasing risk of schizophrenia associated with MTHFR 677 CT+TT genotype was found (OR=1.6, p=0.021). Association was also evaluated by considering the C677T polymorphism as an interaction with COMT Val158Met and ADRA2A C-1291G polymorphisms previously associated with schizophrenia risk using a logistic regression analysis.
  
  
  RESULTS
  Previous studies of MTHFR*COMT (C677T*Val158Met) interaction in relation to schizophrenia resulted in inconsistent results. In our sample this interaction did not significantly differ between schizophrenics and control subjects. On the other hand analysis of MTHFR*ADRA2A (C677T*C-1291G) interaction revealed significant association between ADRA2A CC+CG genotype in the MTHFR TC+TT carriers (p=0.008).
  
  
  CONCLUSIONS
  Our results support role of noradrenergic functions as well as previously proposed role of epigenetic control in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to prove our results.
authors: Laboratory of Neurobiology and Molecular Psychiatry, Laboratory of Molecular Physiology, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors: Jan
authors: J
authors: Lochman
authors: Laboratory of Neurobiology and Molecular Psychiatry, Laboratory of Molecular Physiology, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
authors: Jiří
authors: J
authors: Plesník
authors: Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
authors: Vladimír
authors: V
authors: Janout
authors: Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
authors: Jana
authors: J
authors: Povová
authors: Institute of Animal Physiology and Genetics, Academy of Science, Brno, Czech Republic.
authors: Ivan
authors: I
authors: Míšek
authors: Psychiatric Hospital Jihlava, Jihlava, Czech Republic.
authors: Dagmar
authors: D
authors: Dvořáková
authors: Laboratory of Neurobiology and Molecular Psychiatry, Laboratory of Molecular Physiology, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic. omarsery@sci.muni.cz.
authors: Omar
authors: O
authors: Šerý
mesh_terms: D000328:Adult; D044127:Epigenesis, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C547768:ADRA2A protein, human; D018341:Receptors, Adrenergic, alpha-2; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)