American Journal of Medical Genetics (Neuropsychiatric Genetics) 74:544–545 (1997)

Brief Clinical Report

Serotonin Transporter Gene Regulatory Region
Polymorphism and Anxiety-Related Traits in
the Japanese
Toshiaki Nakamura,1 Taro Muramatsu,1* Yutaka Ono,2 Sachio Matsushita,1 Susumu Higuchi,1
Hiroko Mizushima,2 Kimio Yoshimura,2 Shigenobu Kanba,3 and Masahiro Asai2
1
Department of Psychiatry, Kurihama National Hospital, Kanagawa, Japan
2
Department of Neuropsychiatry, Keio University School of Medicine, Keio, Japan
3
Department of Neuropsychiatry, Yamanashi Medical University, Yamanashi, Japan

INTRODUCTION bution of genotypes in our sample was in Hardy-Wein-

Recently Lesch et al. [1996] reported a positive asso-
ciation between the serotonin transporter (5-HTT)
gene regulatory region polymorphism and anxiety-
related personality. The results of personality analysis
are affected by racial differences as well as by other
confounders such as age and gender. We tried to rep-
licate their findings in a homogenous Japanese popu-
lation. The subjects were 203 healthy Japanese female
students (age 19.57 ± 2.22 years) attending a nursing
junior college. After informed consent was obtained,
venous blood was drawn for genotyping, and the Tem-
perament and Character Inventory (TCI) [Cloninger et
al., 1993; Kijima et al., 1996] and the NEO Personality
Inventory (NEO-PI) [Costa and McCrae, 1989; Shi-
monaka, 1997] were applied to all subjects. The TCI is
an extended version of the Tridimentional Personality
Questionnaire (TPQ), which was used in the study by
Lesch et al. [1996].
Genotyping was performed by PCR according to the
method of Heils et al. [1996], slightly modified, i.e., the
concentration of dNTPs was 150 mmol/l, and 75% of
dGTP was replaced with 7-deazaguanosine. The distri-
berg equilibrium, but was much different from the data
of Lesch et al. [1996]: 139 (68.5%) subjects had the s/s
genotype, 60 (29.6%) had l/s, and 4 (2.0%) had l/l (s,
short allele; l, long allele). Frequency of the long allele
was substantially lower (16.7%) than in Lesch et al.
[1996] (57%).
Tables I and II demonstrate the TCI and NEO-PI
personality factor scores by genotype. The lower fre-
quency of the l/l genotype made it impossible to execute
the same statistical analysis as that of Lesch et al.
[1996], but we could not reveal any association between
the long allele and neuroticism or harm-avoidance.
Thus we concluded that, in the Japanese, the 5-HTT
gene regulatory region polymorphism was not associ-
ated with anxiety-related personality traits.
In general, the Japanese are high in emotional re-
straint and interpersonal sensitivity [Ono et al., 1996],
which is considered to be genetic in origin [Kagan et
al., 1993]. It is noteworthy that the short allele, which
Lesch et al. [1996] demonstrated was associated with
anxiety-related traits, was much more prevalent in the
Japanese than in Caucasians. In the present study, we

TABLE I. 5-HTT Genotype and TCI Factor Scores

TCI factor scores
Genotype Novelty Harm Reward Self- Self-
(n) seeking avoidance dependence Persistence directedness Cooperativeness transcendence
s/s (118) 23.16 ± 5.61 18.14 ± 5.98 17.31 ± 3.48 4.69 ± 1.93 25.59 ± 6.61 30.01 ± 5.63 14.68 ± 4.90
l/s (52) 20.81 ± 5.38 17.21 ± 7.20 17.27 ± 3.17 4.92 ± 2.15 26.79 ± 7.29 29.67 ± 5.02 15.35 ± 6.37
l/l (3) 19.67 ± 7.02 11.67 ± 3.06 16.67 ± 5.13 3.33 ± 2.08 31.33 ± 6.51 30.67 ± 9.45 17.00 ± 4.36

*Correspondence to: Dr. Taro Muramatsu, Department of Psy-

chiatry, Kurihama National Hospital, 5-3-1 Nobi Yokosuka, Ka-
nagawa 239, Japan.
Received 2 May 1997; Revised 18 June 1997

© 1997 Wiley-Liss, Inc.

 5-HTT Gene and Anxiety in Japanese 545

TABLE II. 5-HTT Genotype and NEO-PI Factor Scores

NEO-PI factor scores
Genotype
(n) Neuroticism Extraversion Openness Agreeablenes Conscientiousness
s/s (128) 142.99 ± 9.55 147.59 ± 8.46 148.02 ± 9.13 59.19 ± 5.60 55.86 ± 5.00
l/s (55) 143.29 ± 10.88 150.25 ± 10.13 149.84 ± 10.35 61.42 ± 5.34 56.38 ± 5.85
l/l (3) 137.33 ± 9.45 146.00 ± 6.93 144.33 ± 5.03 60.33 ± 3.21 52.67 ± 6.35

failed to show association between the short allele and
anxiety-related traits in the Japanese. However, a pos-
sible hypothesis is that the higher frequency of this
allele in the Japanese could be a reflection of Japanese
characteristics, which obviously awaits further world-
wide investigations.
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