Preliminary evidence for association between schizophrenia and polymorphisms in the regulatory Regions of the ADRA2A, DRD3 and SNAP-25 Genes
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22940547
DOI
10.1016/j.psychres.2012.08.003
PII: S0165-1781(12)00435-0
Knihovny.cz E-resources
- MeSH
- Receptors, Adrenergic, alpha-2 genetics MeSH
- Adult MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Association Studies MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Likelihood Functions MeSH
- Synaptosomal-Associated Protein 25 genetics MeSH
- Receptors, Dopamine D3 genetics MeSH
- Schizophrenia genetics MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans 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
- DRD3 protein, human MeSH Browser
- Synaptosomal-Associated Protein 25 MeSH
- Receptors, Dopamine D3 MeSH
- SNAP25 protein, human MeSH Browser
The results of linkage and candidate gene association studies have led to a range of hypotheses about the pathogenesis of schizophrenia. We limited our study to polymorphisms in candidate genes involved in dopaminergic and noradrenergic systems, and in the 25KDa synaptosomal-associated protein (SNAP-25) gene that is related to neurotransmitter exocytosis. Eight single nucleotide polymorphisms (SNPs) in regulating or coding regions of genes for the alpha-2A adrenergic receptor (ADRA2A), dopamine receptors D1 and D3 (DRD1 and DRD3), dopamine β-hydroxylase (DBH) and SNAP-25 were genotyped in male patients with schizophrenia (n=192) and in healthy controls (n=213). These polymorphisms were previously associated with schizophrenia. The allelic association between schizophrenia and ADRA2A rs1800544 polymorphism, SNAP-25 rs1503112 polymorphism, and DRD3 rs6280 polymorphism was found in our study. However, only observations for rs1503112 survived correction for multiple testing. Association was also evaluated by considering the polymorphisms as interactions; in this case, a likelihood ratio test (LRT) revealed evidence for association with schizophrenia in four polymorphism combinations: two DRD3*SNAP-25 combinations (rs6280*rs3746544 and rs6280*rs3746544, P=0.02), one ADRA2A*SNAP25 combination (rs1800544*rs3746544) and one ADRA2A*DBH combination (rs1800544*rs2519152). Our results are in agreement with the previously proposed role of DNA polymorphisms involved in dopaminergic, noradrenergic and synaptic functions in the pathogenesis of schizophrenia. Further relevant studies including larger sample size and more markers are needed to confirm our results.
References provided by Crossref.org
Gene-Environment Interactions in Major Mental Disorders in the Czech Republic
