Original Article | Published:

Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics

Journal of Human Genetics volume 52, pages 8691 (2007) | Download Citation


Recent association studies suggest that polymorphisms in the promoter and exon 1 upstream region of the dopamine D4 receptor (DRD4) gene play a functional role in the development of common psychiatric illnesses, although there are also conflicting results. In this study, we re-sequenced this region to identify all genomic variants, and tested them for association with schizophrenia. A total of 570 Japanese schizophrenic cases with matched controls were studied by genotyping all identified/validated common polymorphisms (−1106T>C, −906T>C, −809G>A, −616G>C, −521T>C, −376C>T, −291C>T and 12-bp repeat) and a known microsatellite (120-bp tandem duplication) in the upstream region. A single nucleotide polymorphism (SNP) −809G>A in the promoter region was found to be significantly associated with disease (P=0.018 and 0.032 for allelic and genotypic comparisons, respectively), although not surviving after Bonferroni correction. Logistic regression analysis showed that a combination of the four polymorphisms, −809G>A, −616G>C, −291C>T and the 12-bp repeat, conferred a susceptibility to schizophrenia. These results suggest that the upstream variants have a primary functional effect in the etiology of schizophrenia in the Japanese population.

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  1. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan

    • Mizuho Nakajima
    • , Eiji Hattori
    • , Kazuo Yamada
    • , Yoshimi Iwayama
    • , Tomoko Toyota
    •  & Takeo Yoshikawa
  2. Department of Paediatrics, Tokyo Medical University, Shinjuku, Tokyo 160-0023, Japan

    • Mizuho Nakajima
    •  & Akinori Hoshika
  3. Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan

    • Yasuhide Iwata
    • , Kenji J Tsuchiya
    •  & Genichi Sugihara
  4. Division of Clinical Neuroscience, Chiba University, Center for Forensic Mental Health, Chiba 260-8670, Japan

    • Kenji Hashimoto
  5. Department of Psychiatry, Chiba University, Graduate School of Medicine, Chiba, Japan

    • Hiroyuki Watanabe
    •  & Masaomi Iyo
  6. CREST, Japan Science and Technology Agency, Saitama, Japan

    • Takeo Yoshikawa


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Correspondence to Takeo Yoshikawa.

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