No association between a TPH2 promoter polymorphism and mood disorders or monoamine turnover.
BACKGROUND
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. TPH2 is a recently discovered isoform that is expressed predominantly in serotonin neurons. Associations are reported of TPH2 polymorphisms with MDD, bipolar disorder and suicidal behavior. This study examines a single nucleotide polymorphism in the putative promoter region of the TPH2 gene.


METHODS
One hundred nine bipolar, 324 major depressive disorder, and 130 healthy volunteers were genotyped for the rs4131347 (-C8347G) promoter SNP. Association was assessed with diagnosis, suicide attempt status, severity of psychopathology and cerebrospinal fluid monoamine metabolite levels of 5-HIAA, HVA, and MHPG. General linear models and logistic regression tested the effect of genotype*childhood abuse interactions on psychopathology severity and suicide attempt.


RESULTS
There was no association between genotype and either mood disorder, suicide attempt status, psychopathology severity or CSF monoamine metabolite levels.


CONCLUSIONS
No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function.
Mann
J John
JJ
Department of Neuroscience, New York State Psychiatric Institute, NY 10032, USA. jjm@columbia.edu
Currier
Dianne
D
Murphy
Lauren
L
Huang
Yung-yu
YY
Galfalvy
Hanga
H
Brent
David
D
Greenhill
Laurence
L
Oquendo
Maria
M
D000328:Adult; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002648:Child; D002649:Child Abuse / Q000523:psychology; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013406:Suicide, Attempted / Q000523:psychology; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase; D006719:Homovanillic Acid