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Risk allele for side effects induced by Clozapine identified

Date:
April 6, 2016
Source:
Osaka University
Summary:
Clozapine (CLZ) is a “gold standard” drug for managing treatment-resistant schizophrenia, who do not respond adequately to first-line antipsychotics. However, despite its efficacy, the use of CLZ is significantly restricted by severe side effects, which are rare but potentially life-threatening.
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Manhattan plot for the genome-wide pharmacogenomics results Red line indicates genome-wide significance (5 X 10-8). The Y axis is -log10(P-values) of the SNPs and the X axis is chromosomal position (hg19).
Credit: Image courtesy of Osaka University

Clozapine (CLZ) is a "gold standard" drug for managing treatment-resistant schizophrenia (TRS), who do not respond adequately to first-line antipsychotics.

Despite its efficacy with TRS, the use of CLZ is significantly restricted by severe side effects, such as Clozapine-induced agranulocytosis (CIA) or Clozapine-induced granulocytopenia (CIG), which are rare (CIA: 1% and CIG: 3%) but potentially life-threatening.

Ryota Hashimoto, an associate professor at Osaka University, Nakao Iwata, a professor at Fujita Health University, and Taisei Mushiroda, a group director at RIKEN conducted a genome-wide pharmacogenomic analysis and detected a significant association of HLA-B*59:01 with CIA/CIG (CIAG).

HLA-B*59:01 is one of the alleles of HLA-B gene, which is involved in recognition of 'self' and 'non-self' and induction of immune response. HLA- B*59:01 may be clinically useful as a marker to prioritize the CIG patients who have low risk to develop CIA, by accumulating scientific grounds through prospective clinical studies based on this group's research results. The analysis of functions of HLA-B*59:01 is also essential for the clarification of mechanism for CIAG.


Story Source:

Materials provided by Osaka University. Note: Content may be edited for style and length.


Journal Reference:

  1. Takeo Saito, Masashi Ikeda, Taisei Mushiroda, Takeshi Ozeki, Kenji Kondo, Ayu Shimasaki, Kohei Kawase, Shuji Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kazutaka Ohi, Masatoshi Takeda, Yoichiro Kamatani, Shusuke Numata, Tetsuro Ohmori, Shu-ichi Ueno, Manabu Makinodan, Yosuke Nishihata, Masaharu Kubota, Takemi Kimura, Nobuhisa Kanahara, Naoki Hashimoto, Kiyoshi Fujita, Kiyotaka Nemoto, Taku Fukao, Taro Suwa, Tetsuro Noda, Yuji Yada, Manabu Takaki, Naoya Kida, Taku Otsuru, Masaru Murakami, Atsushi Takahashi, Michiaki Kubo, Ryota Hashimoto, Nakao Iwata. Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population. Biological Psychiatry, 2016; DOI: 10.1016/j.biopsych.2015.12.006

Cite This Page:

Osaka University. "Risk allele for side effects induced by Clozapine identified." ScienceDaily. ScienceDaily, 6 April 2016. <www.sciencedaily.com/releases/2016/04/160406074738.htm>.
Osaka University. (2016, April 6). Risk allele for side effects induced by Clozapine identified. ScienceDaily. Retrieved May 8, 2017 from www.sciencedaily.com/releases/2016/04/160406074738.htm
Osaka University. "Risk allele for side effects induced by Clozapine identified." ScienceDaily. www.sciencedaily.com/releases/2016/04/160406074738.htm (accessed May 8, 2017).