Original Article

Journal of Human Genetics (2001) 46, 26–31; doi:10.1007/s100380170120

Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits

Hiroshi Mitsuyasu1,2, Naotsugu Hirata1, Yasuyoshi Sakai1, Hiroki Shibata1, Yasuhiko Takeda1,2, Hideaki Ninomiya2, Hiroaki Kawasaki2, Nobutada Tashiro2 and Yasuyuki Fukumaki1

  1. 1Division of Disease Genes, Institute of Genetic Information, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  2. 2Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Correspondence: Yasuyuki Fukumaki, Division of Disease Genes, Institute of Genetic Information, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Fax: +81-92-632-2375. E-mail: yfukumak@gen.kyushu-u.ac.jp

Received 28 August 2000; Accepted 25 October 2000.

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Abstract

The human dopamine D4 receptor (DRD4) is of major interest in molecular studies of schizophrenia and personality traits. We examined the association of schizophrenia and polymorphisms in the upstream region of the DRD4 gene (-768G>A in the negative modulator region; -521C>T, -376C>T, and -291C>T in the cell type-specific promoter region; and -616C>G between the two regions) in 208 schizophrenic patients and 210 normal controls. No significant difference in genotype and allele frequencies was observed between the two groups, indicating that these polymorphisms do not make a major contribution to the pathogenesis of schizophrenia. We also studied the association of polymorphisms in the upstream region and a 48-bp repeat polymorphism in exon III of the DRD4 gene with personality traits in 173 Japanese individuals who completed the temperament and character inventory (TCI). The -768G>A polymorphism was significantly associated with reward dependence (P = 0.044), while no significant association was observed between novelty seeking and polymorphisms in the upstream region or the exon III repeat polymorphism of the DRD4 gene.

Keywords:

Dopamine D4 receptor, Polymorphism, Association, Schizophrenia, Personality trait, TCI