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Association Of A Polyadenylation Polymorphism In The Serotonin Transporter And Panic Disorder

Gyawali, Sandeep; Subaran, Ryan; Weissman, Myrna M.; Hershkowitz, Dylan; McKenna, Morgan C.; Talati, Ardesheer; Fyer, Abby J.; Wickramaratne, Priya; Adams, Phillip B.; Hodge, Susan E.; Schmidt, Carl J.; Bannon, Michael J.; Glatt, Charles E.

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 ϭ 65) and lymphoblast cultures (n ϭ 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 ϭ 307) and a control sample (n ϭ 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 Ͻ .001) and lymphoblasts (p Ͻ .001). The balance of the polyadenylation forms is also associated with gender in brain only (p Ͻ .05). Association testing of rs3813034 in PD identified a significant association (p ϭ .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.

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Also Published In

Title
Biological Psychiatry
DOI
https://doi.org/10.1016/j.biopsych.2009.10.015

More About This Work

Academic Units
Epidemiology
Psychiatry
Published Here
February 1, 2022