The tryptophan hydroxylase (TPH) 2 gene unlike TPH-1 exhibits no association with stress-induced depression.
BACKGROUND
Serotonin (5-HT) has been implicated in the pathophysiology of several psychiatric disorders including major depression (MD). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), and might be related to the pathogenesis of MD. Two isoforms are known, TPH-1 and TPH-2. Their association with MD is still debated.


METHODS
A case-control design was used for candidate gene-disease association in 194 patients with stress-induced MD, and 246 healthy controls, all North European Caucasians. Five TPH-2 polymorphisms were analyzed in terms of genotype, allele, and haplotype-based associations.


RESULTS
Neither single marker nor haplotype-based analyses showed significant associations between TPH-2 and MD.


CONCLUSIONS
The interpretations are limited by the restricted population size.


CONCLUSIONS
There was no association between TPH-2 gene variants and MD in the same population that had shown a strong association with TPH-1. Hence, the results suggest that in this particular group of stress-induced depression patients TPH-1 appears to be more relevant to MD pathogenesis than TPH-2.
Gizatullin
Rinat
R
Department of Clinical Neuroscience, Psychiatry Section, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
Zaboli
Ghazal
G
Jönsson
Erik G
EG
Asberg
Marie
M
Leopardi
Rosario
R
D000328:Adult; D003865:Major Depressive Disorder / Q000209:etiology / Q000235:genetics* / Q000523:psychology; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D013315:Stress, Psychological / Q000150:complications* / Q000235:genetics / Q000523:psychology; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D020033:Protein Isoforms; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase