Am J Psychiatry 156:5, May 1999
No Evidence for an Association of Polymorphisms of the
Tryptophan Hydroxylase Gene With Affective Disorders
or Attempted Suicide Among Japanese Patients
Hiroshi Kunugi, M.D., Sugiko Ishida, M.D., Tadafumi Kato, M.D., Toshiyuki Sakai, M.D.,
Masahiko Tatsumi, M.D., Tetsuya Hirose, M.D., and Shinichiro Nanko, M.D.
Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of se-
rotonin. The authors examined whether polymorphisms A218C and A779C in intron 7 of
the tryptophan hydroxylase gene are associated with a risk for affective disorders or sui-
Subjects were 141 patients with bipolar disorder and 73 patients
with unipolar affective disorder, 46 of whom had a history of attempted suicide, and 208
healthy volunteers. All subjects were unrelated to each other, and all were Japanese.
Genotyping was performed by polymerase chain reaction amplification followed by diges-
tion by a restriction enzyme and single-strand conformational polymorphism analysis.
There was no significant genotypic or allelic association of the A218C polymorphism
with bipolar disorder, unipolar depression, or history of attempted suicide. In nearly 100%
of the subjects, genotypes for the A779C were identical to those for the A218C.
The authors conclude that the examined polymorphisms are unlikely to have major
relevance to the pathogenesis of affective disorders or suicidal behavior.
(Am J Psychiatry 1999; 156:774–776)
ryptophan hydroxylase (EC 126.96.36.199) is the rate-
limiting enzyme in the biosynthesis of serotonin. Alter-
ations in the serotonergic system have been implicated
in affective disorders and suicidal behavior (1). A poly-
morphism (A218C) in intron 7 of the tryptophan hy-
droxylase gene was reported to be associated with bi-
polar affective disorder, but not with a history of
attempted suicide (2). Another polymorphism
(A779C) in intron 7 of the tryptophan hydroxylase
gene, which is in tight linkage disequilibrium to the
A218C polymorphism (3), was reported to be associ-
ated with attempted suicide (4, 5) and with 5-hydrox-
yindoleacetic acid concentration in CSF (4). However,
the results were contradictory: the earlier study (4) re-
ported an association between attempted suicide and
the 779C allele, but the later study (5) reported a
greater frequency of the 779A allele among suicide at-
tempters. Abbar et al. (6) found no significant associa-
tion between attempted suicide and the C2-38/AvaII
polymorphism of the tryptophan hydroxylase gene.