Neuroscience Letters 383 (2005) 194–198 The X-box binding protein 1 (XBP1) gene is not associated with methamphetamine dependence Yukitaka Morita a , Hiroshi Ujike a,b,∗ , Yuji Tanaka a,b , Naohiko Uchida a , Akira Nomura a , Kyohei Otani a , Makiko Kishimoto a , Akiko Morio a , Toshiya Inada b,c , Mutsuo Harano b,d , Tokutaro Komiyama b,e , Mitsuhiko Yamada b,f , Yoshimoto Sekine b,g , Nakao Iwata b,h , Masaomi Iyo b,i , Ichiro Sora b,j , Norio Ozaki b,c a Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan b Japanese Genetics Initiative for Drug Abuse, Japan c Department of Psychiatry and Psychobiology, Nagoya University Graduate School of Medicine, Nagoya, Japan d Department of Neuropsychiatry, Kurume University Graduate School of Medicine, Kurume, Japan e Division of Psychiatry, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan f National Institute of Mental Health, National Center of Neurology and Psychiatry, Ichikawa, Japan g Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan h Department of Psychiatry, Fujita Health University School of Medicine, Houmei, Japan i Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan j Division of Psychobiology, Department of Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan Received 3 March 2005; received in revised form 2 April 2005; accepted 4 April 2005 Abstract Bipolar disorder has known as a high risk factor for substance abuse and dependence such as alcohol and illegal drugs. Recently, Kakiuchi et al. reported that the -116C/G polymorphism in the promoter region of the X-box binding protein 1 (XBP-1) gene, which translates a transcription factor specific for endoplasmic reticulum stress caused by misfolded proteins, was associated with bipolar disorders and schizophrenia in a Japanese population. Abuse of methamphetamine often produces affective disorders such as manic state, depressive state, and psychosis resembling paranoid-type schizophrenia. To clarify a possible involvement of XBP-1 in the etiology of methamphetamine dependence, we examined the genetic association of the -116C/G polymorphism of the XBP-1 gene by a case–control study. We found no significant association in allele and genotype frequencies of the polymorphism either with methamphetamine dependence or any clinical phenotype of dependence. Because the polymorphism is located in the promoter region of the XBP-1 gene and affects transcription activity of the gene, it is unlikely that dysfunction of XBP-1 may induces susceptibility to methamphetamine dependence. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Methamphetamine dependence; Genetics; Association study; X-box binding protein 1 Substance abuse has increased dramatically worldwide. The incidence and prevalence of methamphetamine dependence especially has become increasingly widespread both in the Western world and in Asia. In these epidemic phenomena, genetic contributions to the etiology of substance abuse have been demonstrated by family, twin and adoption studies ∗ Corresponding author. Tel.: +81 86 235 7242; fax: +81 86 235 7246. E-mail address: hujike@cc.okayama-u.ac.jp (H. Ujike). [2,13,27]. Kendler et al. [13] showed that twin resemblance increases from occasional use to abuse or dependence in a population-based study of twins. The estimated heritability of cocaine use was 0.39, whereas the heritabilities of its abuse and dependence were 0.79 and 0.65, respectively [14]. Anal- ysis of these data may contribute to the understanding of the significance of genetic involvement in substance abuse. In recent years, bipolar disorders have been focused on as a risk factor for substance abuse. The National Institute of 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.04.014