Association study between Disrupted-in-Schizophrenia-1 (DISC1) and Japanese patients with treatment-resistant schizophrenia (TRS).
Treating the 20-30% of patients with schizophrenia whose symptoms are resistant to antipsychotic treatment, a condition known as treatment-resistant schizophrenia (TRS), can be problematic. Recently, an association between Disrupted-in-Schizophrenia-1 (DISC1), a candidate susceptibility gene for schizophrenia, and TRS was reported. Associations between three missense SNPs, rs3738401 (Q264R), rs6675281 (L607F), and rs821616 (S704C) in DISC1, especially rs3738401, showed strong significance. Thus, the main aim of our current study was to examine if the reported possible functional polymorphisms in DISC1 were related to Japanese TRS. First, DISC1 was re-investigated in 485 Japanese patients with schizophrenia and 660 healthy controls with a case-control study using four candidate SNPs, rs751229, rs3738401, rs821597, and rs821616. DISC1 was not associated with schizophrenia in the Japanese population. Second, we investigated whether these SNPs contributed to TRS in 127 inpatients with schizophrenia (35 patients; TRS and 92 patients; non-TRS). The genotypic distributions of these four SNPs were not significantly different between TRS and non-TRS in either genotypic or recessive models of minor alleles. In addition, clinical variables, such as improvement in clinical symptoms, duration of hospitalization, and total antipsychotics dose amounts, were not different among the genotypes of these SNPs. Taken together, results showed that DISC1 had no apparent degree of association with Japanese patients with schizophrenia as a candidate susceptibility gene for disease per se or TRS.
Juntendo University Schizophrenia Projects, Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.
Yuri
Y
Hotta
Tohru
T
Ohnuma
Ryo
R
Hanzawa
Nobuto
N
Shibata
Hitoshi
H
Maeshima
Hajime
H
Baba
Tokiko
T
Hatano
Yuto
Y
Takebayashi
Maiko
M
Kitazawa
Motoyuki
M
Higa
Toshihito
T
Suzuki
Heii
H
Arai
D000483:Alleles; D014150:Antipsychotic Agents / Q000378:metabolism / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006785:Hospitals, University; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*
D014150:Antipsychotic Agents; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins