Linked Life Data

19725030

Source:http://linkedlifedata.com/resource/pubmed/id/19725030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2009-12-3
pubmed:abstractText
Anxiety is a polygenic condition, and the recently discovered Endocannabinoid System (ECS) is one plausible candidate. Experimental data suggest that the ECS can modulate several neurotransmitter systems, including the serotonergic system, which itself plays a significant role in anxiety. However, to date there is no evidence of gene-gene interactions; indeed genetic studies focusing separately on the two systems provide conflicting data. Thus, the aim of our study was to analyze the interaction of the promoter regions of the serotonin transporter (SLC6A4) and cannabinoid receptor 1 (CNR1) genes on anxiety. We genotyped 706 individuals for the 5-HTTLPR in the SLC6A4 promoter and 4 SNPs located in the CNR1 promoter region. Anxiety was measured by the State-Trait Anxiety Inventory (STAI-S, STAI-T), the anxiety subscale of TEMPS-A (TEMPS-Anx), and the Brief Symptom Inventory (BSI-Anx). Significant 5-HTTLPR x CNR1 promoter-promoter interaction was observed using STAI-T (P = 0.0006) and TEMPS-Anx (P = 0.0013). The risk of high anxiety scores on BSI-Anx was 4.6-fold greater in homozygous 'GG' rs2180619 in combination with homozygous 'SS' 5-HTTLPR (P = 0.0005) compared to other genotypes. The effect of previously described "TGC" haplotype in the alternative promoter of CNR1 depended both on the conventional promoter polymorphism and the 5-HTTLPR. Our haplotype and putative transcription binding profile analyses strongly suggest that certain constellations of CB1-receptor and 5-HTT promoters yield extremely high or low synaptic 5-HT concentrations, and these are associated with an anxious phenotype. In conclusion, genetically determined serotonergic and endocannabinoid dysfunctions could lead to a vulnerability causing anxiety disorders and possibly depression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1552-485X
pubmed:author
pubmed:copyrightInfo
2009 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
150B
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1118-27
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5-HTTLPR affect the anxious phenotype.
pubmed:affiliation
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't