Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease

Ryozo Kuwano; Akinori Miyashita; Hiroyuki Arai; Takashi Asada; Masaki Imagawa; Mikio Shoji; Susumu Higuchi; Katsuya Urakami; Akiyoshi Kakita; Hitoshi Takahashi; Tamao Tsukie; Shinichi Toyabe; Kohei Akazawa; Ichiro Kanazawa; Yasuo Ihara; Akihiko Nunomura; Shigeru Chiba; Satoshi Takahashi; Naoki Tomita; Jyunzo Ito; Haruo Hanyu; Hideo Kimura; Shin Kitamura; Hitoshi Shinotoh; Hiroyuki Iwamoto; Masahiko Takahashi; Yasuo Harigaya; Masaki Ikeda; Masakuni Amari; Takeo Takahashi; Ryoichi Nakano; Masatoyo Nishizawa; Masaichi Suga; Makoto Hasegawa; Yasuhiro Kawase; Kenichi Honda; Toshiro Kumanishi; Yukiyosi Takeuchi; Atsushi Ishikawa; Masahiro Morita; Fumihito Yoshii; Hiroyasu Akatsu; Kenji Kosaka; Masahito Yamada; Tsuyoshi Hamaguchi; Satoshi Masuzugawa; Etsuro Matsubara; Takeshi Kawarabayashi; Takeo Takao; Nobuko Ota; Ken Sasaki; Yoshikatsu Fujisawa; Kenji Nakata; Yosuke Wakutani; Kenji Nakashima; Toshiyuki Hayabara; Terumi Ooya; Mitsuo Takahashi; Tatsuo Yamada; Taihei Miyakawa; Eiichiro Uyama; Takefumi Yuzuriha; Ryuji Nakagawa; Shizushi Yoshimoto; Kayoko Serikawa

doi:10.1093/hmg/ddl142

Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease

Ryozo Kuwano, Akinori Miyashita, Hiroyuki Arai, Takashi Asada, Masaki Imagawa, Mikio Shoji, Susumu Higuchi, Katsuya Urakami, Akiyoshi Kakita, Hitoshi Takahashi, Tamao Tsukie, Shinichi Toyabe, Kohei Akazawa, Ichiro Kanazawa, Yasuo Ihara, Akihiko Nunomura, Shigeru Chiba, Satoshi Takahashi, Naoki Tomita, Jyunzo ItoHaruo Hanyu, Hideo Kimura, Shin Kitamura, Hitoshi Shinotoh, Hiroyuki Iwamoto, Masahiko Takahashi, Yasuo Harigaya, Masaki Ikeda, Masakuni Amari, Takeo Takahashi, Ryoichi Nakano, Masatoyo Nishizawa, Masaichi Suga, Makoto Hasegawa, Yasuhiro Kawase, Kenichi Honda, Toshiro Kumanishi, Yukiyosi Takeuchi, Atsushi Ishikawa, Masahiro Morita, Fumihito Yoshii, Hiroyasu Akatsu, Kenji Kosaka, Masahito Yamada, Tsuyoshi Hamaguchi, Satoshi Masuzugawa, Etsuro Matsubara, Takeshi Kawarabayashi, Takeo Takao, Nobuko Ota, Ken Sasaki, Yoshikatsu Fujisawa, Kenji Nakata, Yosuke Wakutani, Kenji Nakashima, Toshiyuki Hayabara, Terumi Ooya, Mitsuo Takahashi, Tatsuo Yamada, Taihei Miyakawa, Eiichiro Uyama, Takefumi Yuzuriha, Ryuji Nakagawa, Shizushi Yoshimoto, Kayoko Serikawa

HOSP - Internal Medicine

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the ε4 variant of APOE, because about half of AD patients have the APOE-ε3* 3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-ε3* 3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P < 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P = 0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P <0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-ε3*3 genotype or lacking the ε4 allele, and DNMBP may be one of the susceptibility genes for AD.

Original language	English
Pages (from-to)	2170-2182
Number of pages	13
Journal	Human Molecular Genetics
Volume	15
Issue number	13
DOIs	https://doi.org/10.1093/hmg/ddl142
Publication status	Published - 2006 Jul

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10.1093/hmg/ddl142

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Kuwano, R., Miyashita, A., Arai, H., Asada, T., Imagawa, M., Shoji, M., Higuchi, S., Urakami, K., Kakita, A., Takahashi, H., Tsukie, T., Toyabe, S., Akazawa, K., Kanazawa, I., Ihara, Y., Nunomura, A., Chiba, S., Takahashi, S., Tomita, N., ... Serikawa, K. (2006). Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease. Human Molecular Genetics, 15(13), 2170-2182. https://doi.org/10.1093/hmg/ddl142

@article{b90c3c7d68c54ffea20a67a23c579d6a,

title = "Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease",

abstract = "The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the ε4 variant of APOE, because about half of AD patients have the APOE-ε3* 3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-ε3* 3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P < 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P = 0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P <0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-ε3*3 genotype or lacking the ε4 allele, and DNMBP may be one of the susceptibility genes for AD.",

author = "Ryozo Kuwano and Akinori Miyashita and Hiroyuki Arai and Takashi Asada and Masaki Imagawa and Mikio Shoji and Susumu Higuchi and Katsuya Urakami and Akiyoshi Kakita and Hitoshi Takahashi and Tamao Tsukie and Shinichi Toyabe and Kohei Akazawa and Ichiro Kanazawa and Yasuo Ihara and Akihiko Nunomura and Shigeru Chiba and Satoshi Takahashi and Naoki Tomita and Jyunzo Ito and Haruo Hanyu and Hideo Kimura and Shin Kitamura and Hitoshi Shinotoh and Hiroyuki Iwamoto and Masahiko Takahashi and Yasuo Harigaya and Masaki Ikeda and Masakuni Amari and Takeo Takahashi and Ryoichi Nakano and Masatoyo Nishizawa and Masaichi Suga and Makoto Hasegawa and Yasuhiro Kawase and Kenichi Honda and Toshiro Kumanishi and Yukiyosi Takeuchi and Atsushi Ishikawa and Masahiro Morita and Fumihito Yoshii and Hiroyasu Akatsu and Kenji Kosaka and Masahito Yamada and Tsuyoshi Hamaguchi and Satoshi Masuzugawa and Etsuro Matsubara and Takeshi Kawarabayashi and Takeo Takao and Nobuko Ota and Ken Sasaki and Yoshikatsu Fujisawa and Kenji Nakata and Yosuke Wakutani and Kenji Nakashima and Toshiyuki Hayabara and Terumi Ooya and Mitsuo Takahashi and Tatsuo Yamada and Taihei Miyakawa and Eiichiro Uyama and Takefumi Yuzuriha and Ryuji Nakagawa and Shizushi Yoshimoto and Kayoko Serikawa",

note = "Funding Information: We thank Professor Shoji Tsuji, Department of Neurology, and Professor Katsushi Tokunaga, Department of Human Genetics, University of Tokyo, for the critical discussion about human molecular genetics. We also thank N. Takei, K. Horigome, A. Kitamura, M. Hirose, Y. Satoh, A. Hirokawa, T. Hosino, S. Yanagihara, K. Takadono, M. Saitoh and N. Yahata for the technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (C)— Advanced Brain Science Project—from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Y.I.).",

year = "2006",

month = jul,

doi = "10.1093/hmg/ddl142",

language = "English",

volume = "15",

pages = "2170--2182",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "13",

}

Kuwano, R, Miyashita, A, Arai, H, Asada, T, Imagawa, M, Shoji, M, Higuchi, S, Urakami, K, Kakita, A, Takahashi, H, Tsukie, T, Toyabe, S, Akazawa, K, Kanazawa, I, Ihara, Y, Nunomura, A, Chiba, S, Takahashi, S, Tomita, N, Ito, J, Hanyu, H, Kimura, H, Kitamura, S, Shinotoh, H, Iwamoto, H, Takahashi, M, Harigaya, Y, Ikeda, M, Amari, M, Takahashi, T, Nakano, R, Nishizawa, M, Suga, M, Hasegawa, M, Kawase, Y, Honda, K, Kumanishi, T, Takeuchi, Y, Ishikawa, A, Morita, M, Yoshii, F, Akatsu, H, Kosaka, K, Yamada, M, Hamaguchi, T, Masuzugawa, S, Matsubara, E, Kawarabayashi, T, Takao, T, Ota, N, Sasaki, K, Fujisawa, Y, Nakata, K, Wakutani, Y, Nakashima, K, Hayabara, T, Ooya, T, Takahashi, M, Yamada, T, Miyakawa, T, Uyama, E, Yuzuriha, T, Nakagawa, R, Yoshimoto, S & Serikawa, K 2006, 'Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease', Human Molecular Genetics, vol. 15, no. 13, pp. 2170-2182. https://doi.org/10.1093/hmg/ddl142

TY - JOUR

T1 - Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease

AU - Kuwano, Ryozo

AU - Miyashita, Akinori

AU - Arai, Hiroyuki

AU - Asada, Takashi

AU - Imagawa, Masaki

AU - Shoji, Mikio

AU - Higuchi, Susumu

AU - Urakami, Katsuya

AU - Kakita, Akiyoshi

AU - Takahashi, Hitoshi

AU - Tsukie, Tamao

AU - Toyabe, Shinichi

AU - Akazawa, Kohei

AU - Kanazawa, Ichiro

AU - Ihara, Yasuo

AU - Nunomura, Akihiko

AU - Chiba, Shigeru

AU - Takahashi, Satoshi

AU - Tomita, Naoki

AU - Ito, Jyunzo

AU - Hanyu, Haruo

AU - Kimura, Hideo

AU - Kitamura, Shin

AU - Shinotoh, Hitoshi

AU - Iwamoto, Hiroyuki

AU - Takahashi, Masahiko

AU - Harigaya, Yasuo

AU - Ikeda, Masaki

AU - Amari, Masakuni

AU - Takahashi, Takeo

AU - Nakano, Ryoichi

AU - Nishizawa, Masatoyo

AU - Suga, Masaichi

AU - Hasegawa, Makoto

AU - Kawase, Yasuhiro

AU - Honda, Kenichi

AU - Kumanishi, Toshiro

AU - Takeuchi, Yukiyosi

AU - Ishikawa, Atsushi

AU - Morita, Masahiro

AU - Yoshii, Fumihito

AU - Akatsu, Hiroyasu

AU - Kosaka, Kenji

AU - Yamada, Masahito

AU - Hamaguchi, Tsuyoshi

AU - Masuzugawa, Satoshi

AU - Matsubara, Etsuro

AU - Kawarabayashi, Takeshi

AU - Takao, Takeo

AU - Ota, Nobuko

AU - Sasaki, Ken

AU - Fujisawa, Yoshikatsu

AU - Nakata, Kenji

AU - Wakutani, Yosuke

AU - Nakashima, Kenji

AU - Hayabara, Toshiyuki

AU - Ooya, Terumi

AU - Takahashi, Mitsuo

AU - Yamada, Tatsuo

AU - Miyakawa, Taihei

AU - Uyama, Eiichiro

AU - Yuzuriha, Takefumi

AU - Nakagawa, Ryuji

AU - Yoshimoto, Shizushi

AU - Serikawa, Kayoko

N1 - Funding Information: We thank Professor Shoji Tsuji, Department of Neurology, and Professor Katsushi Tokunaga, Department of Human Genetics, University of Tokyo, for the critical discussion about human molecular genetics. We also thank N. Takei, K. Horigome, A. Kitamura, M. Hirose, Y. Satoh, A. Hirokawa, T. Hosino, S. Yanagihara, K. Takadono, M. Saitoh and N. Yahata for the technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (C)— Advanced Brain Science Project—from the Ministry of Education, Culture, Sports, Science and Technology, Japan (Y.I.).

PY - 2006/7

Y1 - 2006/7

N2 - The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the ε4 variant of APOE, because about half of AD patients have the APOE-ε3* 3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-ε3* 3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P < 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P = 0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P <0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-ε3*3 genotype or lacking the ε4 allele, and DNMBP may be one of the susceptibility genes for AD.

AB - The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the ε4 variant of APOE, because about half of AD patients have the APOE-ε3* 3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-ε3* 3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P < 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P = 0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P <0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-ε3*3 genotype or lacking the ε4 allele, and DNMBP may be one of the susceptibility genes for AD.

UR - http://www.scopus.com/inward/record.url?scp=33745282142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745282142&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddl142

DO - 10.1093/hmg/ddl142

M3 - Article

C2 - 16740596

AN - SCOPUS:33745282142

SN - 0964-6906

VL - 15

SP - 2170

EP - 2182

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 13

ER -

Dynamin-binding protein gene on chromosome 10q is associated with late-onset Alzheimer's disease

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