Interactive effect of MTHFR and ADRA2A gene polymorphisms on pathogenesis of schizophrenia
Language English Country Sweden Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24522021
PII: NEL340813A07
Knihovny.cz E-resources
- MeSH
- Receptors, Adrenergic, alpha-2 genetics MeSH
- Adult MeSH
- Epigenesis, Genetic genetics MeSH
- Genetic Predisposition to Disease epidemiology genetics MeSH
- Genotype MeSH
- Middle Aged MeSH
- Humans MeSH
- Methylenetetrahydrofolate Reductase (NADPH2) genetics MeSH
- Young Adult MeSH
- Polymorphism, Genetic MeSH
- Risk Factors MeSH
- Schizophrenia epidemiology genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ADRA2A protein, human MeSH Browser
- Receptors, Adrenergic, alpha-2 MeSH
- Methylenetetrahydrofolate Reductase (NADPH2) MeSH
- MTHFR protein, human MeSH Browser
OBJECTIVES: 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.
Gene-Environment Interactions in Major Mental Disorders in the Czech Republic
