Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder

Akira Yoshimi, Nagahide Takahashi, Shinichi Saito, Yoshihito Ito, Branko Aleksic, Hinako Usui, Yukiko Kawamura, Yukari Waki, Takeo Yoshikawa, Tadafumi Kato, Nakao Iwata, Toshiya Inada, Yukihiro Noda, Norio Ozaki

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16 Citations (Scopus)

Abstract

Several lines of evidence, including genome-wide linkage scans and postmortem brain studies of patients with schizophrenia or bipolar disorder, have suggested that DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa), a key regulatory molecule in the dopaminergic signaling pathway, is involved in these disorders. After evaluating the linkage disequilibrium pattern of the gene encoding DARPP-32 (PPP1R1B; located on 17q12), we conducted association analyses of this gene with schizophrenia and bipolar disorder. Single-marker and haplotypic analyses of four single nucleotide polymorphisms (SNPs; rs879606, rs12601930, rs907094, and rs3764352) in a sample set (subjects with schizophrenia = 384, subjects with bipolar disorder = 318, control subjects = 384) showed that PPP1R1B polymorphisms were not significantly associated with schizophrenia, whereas, even after Bonferroni corrections, significant associations with bipolar disorder were observed for rs12601930 (corrected genotypic p = 0.00059) and rs907094 (corrected allelic p = 0.040). We, however, could not confirm these results in a second independent sample set (subjects with bipolar disorder = 366, control subjects = 370). We now believe that the significant association observed with the first sample set was a result of copy number aberrations in the region surrounding these SNPs. Our findings suggest that PPP1R1B SNPs are unlikely to be related to the development of schizophrenia and bipolar disorder in the Japanese population.

Original languageEnglish
Pages (from-to)334-341
Number of pages8
JournalSchizophrenia Research
Volume100
Issue number1-3
DOIs
Publication statusPublished - 03-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

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