Faculty Profiles - ALEKSIC Branko

Papers - ALEKSIC Branko

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A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population Reviewed

Yoshihito Ito, Yukako Nakamura, Nagahide Takahashi, Shinichi Saito, Branko Aleksic, Nakao Iwata, Toshiya Inada, Norio Ozaki

NEUROSCIENCE LETTERS Vol. 438 ( 1 ) page： 70 - 75 2008.6

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primarily expressed in the brain. Phosphohippolin modulates the kinetic activity of Na,K-ATPase and has long-term physiological importance in maintaining cation homeostasis. A recent study reported that FXYD6 was associated with schizophrenia in the United Kingdom samples. Applying the gene-based association concept, we carried out an association study regarding FXYD6 and schizophrenia in a Japanese population, with a sample consisting of 2026 subjects (906 schizophrenics and 1120 controls). After linkage disequilibrium analysis, 23 single nucleotide polymorphisms (SNPs) were genotyped using 5'-exonuclease allelic discrimination assay. We found a significant association of two SNPs (rs11216573; genotypic P value: 0.022 and rs555577; genotypic P value: 0.026, allelic P value: 0.011, uncorrected). Nominal P values did not survive correction for multiple testing (rs11216573; genotypic P value: 0.47 and rs555577; genotypic P value: 0.55, allelic P value: 0.24, after SNPSpD correction). No association was observed between schizophrenia patients and controls in allelic, genotypic and haplotypic analyses. Our findings suggest that FXYD6 is unlikely to be related to the development of schizophrenia in a Japanese population. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2008.04.010

Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample Reviewed

Masashi Ikeda, Nagahide Takahashi, Shinichi Saito, Branko Aleksic, Yuichiro Watanabe, Ayako Nunokawa, Yoshio Yamanouchi, Tsuyoshi Kitajima, Yoko Kinoshita, Taro Kishi, Kunihiro Kawashima, Ryota Hashimoto, Hiroshi Ujike, Toshiya Inada, Toshiyuki Someya, Masatoshi Takeda, Norio Ozaki, Nakao Iwata

SCHIZOPHRENIA RESEARCH Vol. 101 ( 1-3 ) page： 1 - 8 2008.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Systematic linkage disequilibrium (LD) mapping of 8p12-21 in the Icelandic population identified neuregulin 1 (NRG1) as a pdrne candidate gene for schizophrenia. However, results of replication studies have been inconsistent, and no large sample analyses have been reported. Therefore, we designed this study with the aim of assessing this putative association between schizophrenia and NRG1 (especially HAP(ICE) region and exon region) using a gene-based association approach in the Japanese population.
This study was a two-stage association analysis with a different panel of samples, in which the significant association found in the first-set screening samples (1126 cases and 1022 controls) was further assessed in the confirmation samples (1262 cases and 1172 controls, and 166 trio samples). In the first-set scan, 60 SNPs (49 tagging SNPs from HapMap database, four SNPs from other papers, and seven SNPs detected in the mutation scan) were examined.
One haplotype showed a significant association in the first-set screening samples (Global P-value= 0.0244, uncorrected). However, we could not replicate this association in the following independent confirmation samples. Moreover, we could not find sufficient evidence for association of the haplotype identified as being significant in the first-set samples by imputing ungenotyped SNPs from HapMap database.
These results indicate that the positionally and functionally attractive regions of NRG1 are unlikely to contribute to susceptibility to schizophrenia in the Japanese population. Moreover, the nature of our results support that two-stage analysis with large sample size is appropriate to examine the susceptibility genes for common diseases. (C) 2008 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2008.01.010

An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population. Invited Reviewed

Saito S, Takahashi N, Maeno N, Ito Y, Aleksic B, Usui H, Iidaka T, Inada T, Ozaki N

Neuroreport Vol. 19 ( 4 ) page： 471-3 2008.3

An association study of tachykinin receptor 3 gene with schizophrenia in the Japanese population Reviewed International journal

Saito Shinichi, Takahashi Nagahide, Maeno Nobuhisa, Ito Yoshihito, Aleksic Branko, Usui Hinako, Iidaka Tetsuya, Inada Toshiya, Ozaki Norio

NEUROREPORT Vol. 19 ( 4 ) page： 471 - 473 2008.3

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

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

SCHIZOPHRENIA RESEARCH Vol. 100 ( 1-3 ) page： 334 - 341 2008.3

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

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. (c) 2007 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2007.10.028

An association between serotonin receptor 3B gene (HTR3B) and treatment-resistant schizophrenia (TRS) in a Japanese population. Reviewed

Xiaofei Ji, Nagahide Takahashi, Aleksic Branko, Ryoko Ishihara, Taku Nagai, Akihiro Mouri, Shinichi Saito, Nobuhisa Maeno, Toshiya Inada, Norio Ozaki

Nagoya journal of medical science Vol. 70 ( 1-2 ) page： 11 - 7 2008.3

Language：English Publishing type：Research paper (scientific journal)

Genetic factors are thought to be involved in the development of treatment-resistant schizophrenia (TRS). Since several antipsychotic drugs inhibit the release of neurotransmitters via the serotonin receptors 3 (5-HT3), a dysfunction of this kind of receptor might be associated with the development of TRS. Thus, single-marker and haplotype analyses of the tag-single nucleotide polymorphisms (SNPs) of the 5-HT3B subunit gene (HTR3B) were performed in TRS (n = 101) and non-TRS (n = 244) patients. The deletion allele at the 3 bp-insertion/deletion polymorphism site (-100_-102delAAG) located in the putative HTR3B promoter region is significantly more frequent in the TRS group than the insertion allele by a single-marker comparison (p = 0.031). In addition, luciferase promoter assays showed that the deletion allele exhibited significantly higher transcriptional activity than the insertion allele in COS7 cells (p < 0.05). These results suggest that HTR3B is involved in the development of TRS in the Japanese population.

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Association analysis of MTHFR gene in schizophrenia Reviewed International journal

Y. Kawamura, N. Takahashi, S. Saito, H. Usui, A. Yoshimi, Y. Ito, A. Branko, R. Ishihara, K. Yoshida, T. Iidaka, T. Inada, N. Iwata, Y. Noda, N. Ozaki

PSYCHIATRY AND CLINICAL NEUROSCIENCES Vol. 62 ( 1 ) page： S4 - S5 2008.2

Association Study of the Calcineurin A Gamma Subunit Gene (PPP3CC) and Methamphetamine-Use Disorder in a Japanese Population A Collaborative Study by the Japanese Genetics Initiative for Drug Abuse Reviewed International journal

Y. Kinoshita, M. Ikeda, H. Ujike, T. Kitajima, Y. Yamanouchi, B. Aleksic, T. Kishi, K. Kawashima, T. Ohkouchi, N. Ozaki, T. Inada, M. Harano, T. Komiyama, T. Hori, M. Yamada, Y. Sekine, M. Iyo, I. Sora, N. Iwata

DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES Vol. 1139 page： 57 - 62 2008

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Several lines of evidence from animal and genetic analyses showed that the calcineurin A gamma subunit gene (PPP3CC) plays an important role in the pathogenesis of schizophrenia. Moreover, a recent large Japanese case-control study confirmed the genetic association of PPP3CC with schizophrenia. The symptoms of methamphetamine (MAP)-induced psychosis are similar to those of schizophrenia, suggesting that PPP3CC is an attractive candidate gene not only for schizophrenia, but also for METH-related disorders. In this study, we carried out a genetic association study of PPP3CC with MAP-use disorder in a Japanese population. We selected five haplotype-tagging SNPs from the aforementioned replication study and genotyped 393 samples (MAP abuse, 128; control, 265). We could not detect a significant association of all tagging SNPs with each condition. In conclusion, our data suggest that PPP3CC does not elevate the risk of MAP-use disorder in the Japanese population.

DOI： 10.1196/annals.1432.021

Gap junction, bipolar disorder and schizophrenia: Genetic association study Reviewed International journal

Branko Aleksic, Masashi Ikeda, Ryoko Ishihara, Nagahide Takahashi, Sinichi Saito, Atsushi Matsumoto, Toshiya Inada, Tetsuya Idaka, Nakao Iwata, Norio Ozaki

NEUROSCIENCE RESEARCH Vol. 61 page： S219 - S219 2008

Association of SOX10 with schizophrenia in the Japanese population. Invited Reviewed

Maeno N, Takahashi N, Saito S, Ji X, Ishihara R, Aoyama N, Branko A, Miura H, Ikeda M, Suzuki T, Kitajima T, Yamanouchi Y, Kinoshita Y, Iwata N, Inada T, Ozaki N

Psychiatric genetics Vol. 17 ( 4 ) page： 227-31 2007.8

Association of SOX10 with schizophrenia in the Japanese population

Maeno Nobuhisa, Takahashi Nagahide, Saito Shinichi, Ji Xiaofei, Ishihara Ryoko, Aoyama Nagisa, Branko Aleksic, Miura Hideki, Ikeda Masashi, Suzuki Tatsuyo, Kitajima Tsuyoshi, Yamanouchi Yoshio, Kinoshita Yoko, Iwata Nakao, Inada Toshiya, Ozaki Norio

PSYCHIATRIC GENETICS Vol. 17 ( 4 ) page： 227-231 2007.8

Gap junction coding genes and schizophrenia: a genetic association study Reviewed

Branko Aleksic, Ryoko Ishihara, Nagahide Takahashi, Nobuhisa Maeno, Xiaofei Ji, Shinichi Saito, Toshiya Inada, Norio Ozaki

JOURNAL OF HUMAN GENETICS Vol. 52 ( 6 ) page： 498 - 501 2007.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER TOKYO

The aim of this study was to evaluate the association of genes that encode gap junction forming proteins and schizophrenia. Representative genetic candidates (Panx2 and Cx36) from two families of gap junction genes were selected for analysis. According to the present findings these genes represent both functional and positional candidates for schizophrenia. The sample was comprised of 381 schizophrenic patients, and the same number of matched controls was tested in this study in order to evaluate the possible influence of the aforementioned genes on the pathogenesis of schizophrenia. Four SNPs in the case of Panx2 and two SNPs in the case of Cx36 were selected for analysis. Allele-, genotype- and haplotype-wise association did not yield statistically significant results. These data do not suggest that Panx2 or Cx36 could increase the risk of schizophrenia in the Japanese population.

DOI： 10.1007/s10038-007-0142-5

Association study between the transferrin gene and schizophrenia in the Japanese population. Invited Reviewed

Maeno N, Takahashi N, Saito S, Ji X, Branko A, Ishihara R, Yoshida K, Inada T, Iidaka T, Ozaki N

Neuroreport Vol. 18 ( 5 ) page： 517-20 2007.3

Association study between the transferrin gene and schizophrenia in the Japanese population

Maeno Nobuhisa, Takahashi Nagahide, Saito Shinichi, Ji Xiaofei, Branko Aleksic, Ishihara Ryoko, Yoshida Keizo, Inada Toshiya, Iidaka Tetsuya, Ozaki Norio

NEUROREPORT Vol. 18 ( 5 ) page： 517-520 2007.3

Biological research of schizophrenia-Recent advance in diffusion tensor imaging and gamma band activity

IIDAKA Tetsuya, BRANKO Aleksic, SAITO Shinichi, MAENO Nobuhisa, OZAKI Norio

Vol. 17 ( 4 ) page： 311 - 317 2006.12

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