A tryptophan hydroxylase gene marker for suicidality and alcoholism.
BACKGROUND
Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. Low turnover rate of this monoamine neurotransmitter is associated with impaired impulse control. We previously reported that, in Finns, TPH genotype was associated with suicidality, a pathophysiological mechanism that may involve impaired impulse control.


METHODS
Association and sib-pair linkage analyses of a polymorphism in intron 7 of the TPH gene with suicidality, alcoholism, and the Karolinska Scales of Personality were conducted in 804 Finnish alcoholic offenders, controls, and their relatives, in a sample that included 369 sib pairs.


RESULTS
The association of the TPH 17 779C (L) allele to suicidality in impulsive offenders reported previously was replicated in a new group of Finnish offenders (P=.001, n=122). The intron 7 variant in the TPH gene showed significant evidence for linkage to suicidality (P=.006 in unaffected sib pairs), severe suicide attempts (P=.006 in unaffected sib pairs; regression: P=.01), alcoholism (P=.003 in unaffected sib-pairs; regression: P=.02), and Karolinska Scales of Personality socialization score (regression: P=.002).


CONCLUSIONS
The status of the TPH A779C allele as a marker for suicidality was replicated and linkage with alcoholism and Karolinska Scales of Personality socialization score was also observed. A functional variant(s) in or close to the TPH gene may predispose individuals to suicidality and other behaviors thought to be influenced by serotonin.
Section of Molecular Genetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. nielsen@helix.nih.gov
D A
DA
Nielsen
M
M
Virkkunen
J
J
Lappalainen
M
M
Eggert
G L
GL
Brown
J C
JC
Long
D
D
Goldman
M
M
Linnoila
D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005387:Finland / Q000453:epidemiology; D008040:Genetic Linkage; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008957:Models, Genetic; D010551:Personality / Q000145:classification / Q000235:genetics; D011110:Polymorphism, Genetic; D011329:Prisoners / Q000706:statistics & numerical data; D012044:Regression Analysis; D012701:Serotonin / Q000235:genetics; D013406:Suicide, Attempted / Q000145:classification / Q000706:statistics & numerical data*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D005819:Genetic Markers; D012701:Serotonin; D014365:Tryptophan Hydroxylase