Genetic variations in tryptophan hydroxylase in suicidal behavior: analysis and meta-analysis.
BACKGROUND
Neurobiological studies implicate serotonergic dysfunction in suicidal behavior. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin, plays a vital role in serotonin metabolism. Thus, variations in the TPH gene have been regarded as prime candidates in the susceptibility to suicidal behavior. The most widely studied genetic variations in the TPH gene, which are located in intron 7, yielded conflicting results in individual studies on suicide-related behavior.


METHODS
We performed a meta-analysis on a total of 898 patients and 1179 control subjects, in addition to our local association study in consecutively recruited suicide attempters (n=147) and healthy control subjects of German descent (n=326).


RESULTS
We observed a nonsignificant higher frequency of the TPH intron 7 A218 allele in our local group. The meta-analysis showed a weak yet highly significant increase in the frequency of the A218 allele (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.17-1.50; p=.00002) and an over-representation of A-carriers (OR: 1.48; 95% CI: 1.22-1.79; p=.00005) in Caucasian suicide attempters/victims.


CONCLUSIONS
Our meta-analysis provides strong evidence for an association of suicide-related behavior with an A218 single-nucleotide polymorphism in the TPH gene in Caucasians. Because this variation do not seem to alter functional properties of the TPH gene or protein, functional variations remain to be identified and subsequently tested for association with suicide-related behavior.
Rujescu
Dan
D
Division of Molecular Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Giegling
Ina
I
Sato
Tetsuya
T
Hartmann
Annette M
AM
Möller
Hans Jürgen
HJ
D000328:Adult; D000368:Aged; D000483:Alleles; D001526:Behavioral Symptoms / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012701:Serotonin / Q000235:genetics; D013405:Suicide; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People
D012701:Serotonin; D014365:Tryptophan Hydroxylase