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Biol Psychiatry. 2010 Feb 15;67(4):331-8. doi: 10.1016/j.biopsych.2009.10.015. Epub 2009 Dec 6.

Association of a polyadenylation polymorphism in the serotonin transporter and panic disorder.

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  • 1Department of Psychiatry, Weill Medical College of Cornell University, New York, New York, USA.

Abstract

BACKGROUND:

Genetic markers in the serotonin transporter are associated with panic disorder (PD). The associated polymorphisms do not include the serotonin transporter-linked polymorphic region and display no obvious functional attributes. A common polymorphism (rs3813034) occurs in one of the two reported polyadenylation signals for the serotonin transporter and is in linkage disequilibrium with the PD-associated markers. If functional, rs3813034 might be the risk factor that explains the association of the serotonin transporter and PD.

METHODS:

Quantitative polymerase chain reaction on human brain samples (n = 65) and lymphoblast cultures (n = 71) was used to test rs3813034 for effects on expression of the polyadenylation forms of the serotonin transporter. rs3813034 was also tested for association in a sample of PD cases (n = 307) and a control sample (n = 542) that has similar population structure.

RESULTS:

The balance of the two polyadenylation forms of the serotonin transporter is associated with rs3813034 in brain (p < .001) and lymphoblasts (p < .001). The balance of the polyadenylation forms is also associated with gender in brain only (p < .05). Association testing of rs3813034 in PD identified a significant association (p = .0068) with a relative risk of 1.56 and 1.81 for the heterozygous and homozygous variant genotypes, respectively.

CONCLUSIONS:

rs3813034 is a functional polymorphism in the serotonin transporter that alters the balance of the two polyadenylation forms of the serotonin transporter. rs3813034 is a putative risk factor for PD and other behavioral disorders that involve dysregulation of serotonergic neurotransmission.

2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PMID:
19969287
[PubMed - indexed for MEDLINE]
PMCID:
PMC2980348
Free PMC Article

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