Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder.
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.
Division of Clinical Science and Neuropsychopharmacology, Graduate School of Pharmacy, Meijo University, Aichi, 468-8503, Japan.
Akira
A
Yoshimi
Nagahide
N
Takahashi
Shinichi
S
Saito
Yoshihito
Y
Ito
Branko
B
Aleksic
Hinako
H
Usui
Yukiko
Y
Kawamura
Yukari
Y
Waki
Takeo
T
Yoshikawa
Tadafumi
T
Kato
Nakao
N
Iwata
Toshiya
T
Inada
Yukihiro
Y
Noda
Norio
N
Ozaki
D044466:Asian People / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000235:genetics / Q000502:physiology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics* / Q000502:physiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004298:Dopamine