Association of a polyadenylation polymorphism in the serotonin transporter and panic disorder.
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.
Gyawali
Sandeep
S
Department of Psychiatry, Weill Medical College of Cornell University, New York, New York, USA.
Subaran
Ryan
R
Weissman
Myrna M
MM
Hershkowitz
Dylan
D
McKenna
Morgan C
MC
Talati
Ardesheer
A
Fyer
Abby J
AJ
Wickramaratne
Priya
P
Adams
Phillip B
PB
Hodge
Susan E
SE
Schmidt
Carl J
CJ
Bannon
Michael J
MJ
Glatt
Charles E
CE
D000818:Animals; D001921:Brain / Q000378:metabolism; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D016584:Panic Disorder / Q000235:genetics* / Q000473:pathology; D026723:Polyadenylation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012737:Sex Factors; D013223:Statistics as Topic
D050486:Serotonin Plasma Membrane Transport Proteins