Lack of Genetic Association Between TREM2 and Late-Onset Alzheimer's Disease in a Japanese Population

Article type: Short Communication

Authors: Miyashita, Akinori^{a; *} | Wen, Yanan^a | Kitamura, Nobutaka^b | Matsubara, Etsuro^{c; 1} | Kawarabayashi, Takeshi^c | Shoji, Mikio^c | Tomita, Naoki^d | Furukawa, Katsutoshi^d | Arai, Hiroyuki^d | Asada, Takashi^e | Harigaya, Yasuo^f | Ikeda, Masaki^g | Amari, Masakuni^g | Hanyu, Haruo^h | Higuchi, Susumuⁱ | Nishizawa, Masatoyo^j | Suga, Masaichi^k | Kawase, Yasuhiro^l | Akatsu, Hiroyasu^{m; 2} | Imagawa, Masakiⁿ | Hamaguchi, Tsuyoshi^o | Yamada, Masahito^o | Morihara, Takashi^p | Takeda, Masatoshi^p | Takao, Takeo^q | Nakata, Kenji^r | Sasaki, Ken^r | Watanabe, Ken^s | Nakashima, Kenji^t | Urakami, Katsuya^u | Ooya, Terumi^v | Takahashi, Mitsuo^w | Yuzuriha, Takefumi^x | Serikawa, Kayoko^y | Yoshimoto, Seishi^y | Nakagawa, Ryuji^y | Saito, Yuko^z | Hatsuta, Hiroyuki^aa | Murayama, Shigeo^aa | Kakita, Akiyoshi^bb | Takahashi, Hitoshi^bb | Yamaguchi, Haruyasu^cc | Akazawa, Kohei^b | Kanazawa, Ichiro^dd | Ihara, Yasuo^ee | Ikeuchi, Takeshi^a | Kuwano, Ryozo^{a; *}

Affiliations: [a] Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan | [b] Department of Medical Informatics, Niigata University, Niigata, Japan | [c] Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan | [d] Department of Geriatric and Complementary Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan | [e] Department of Psychiatry, University of Tsukuba, Tsukuba, Japan | [f] Department of Neurology, Maebashi Red Cross Hospital, Maebashi, Japan | [g] Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan | [h] Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan | [i] Division of Clinical Research, Kurihama Alcoholism Center, Yokosuka, Japan | [j] Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan | [k] Higashi Niigata Hospital, Niigata, Japan | [l] Kawase Neurology Clinic, Sanjo, Japan | [m] Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan | [n] Imagawa Clinic, Osaka, Japan | [o] Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan | [p] Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan | [q] Kurashiki Heisei Hospital, Kurashiki, Japan | [r] Kinoko Espoir Hospital, Kasaoka, Japan | [s] Watanabe Hospital, Tottori, Japan | [t] Department of Neurology, Tottori University, Yonago, Japan | [u] Department of Biological Regulation, Section of Environment and Health Science, Tottori University, Yonago, Japan | [v] Town Office, Onan, Japan | [w] Department of Clinical Pharmacology, Fukuoka University, Fukuoka, Japan | [x] Department of Psychiatry, National Hospital Organization, Hizen Psychiatric Center, Saga, Japan | [y] Ureshino-Onsen Hospital, Saga, Japan | [z] Department of Pathology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan | [aa] Department of Neuropathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan | [bb] Department of Pathology, Brain Research Institute, Niigata University, Niigata, Japan | [cc] Graduate School of Health Sciences, Gunma University, Maebashi, Japan | [dd] National Center Hospital of Neurology and Psychiatry, Tokyo, Japan | [ee] Department of Neuropathology, Doshisha University, Kizugawa, Japan

Correspondence: [*] Correspondence to: Ryozo Kuwano, 1-757 Asahimachi, Chuo-ku, Niigata, Niigata 951-8585, Japan. Tel.: +81 25 227 2274; Fax: +81 25 227 0793; E-mail: ryosun@bri.niigata-u.ac.jp (R. Kuwano); and Akinori Miyashita, 1-757 Asahimachi, Chuo-ku, Niigata 951-8585, Japan. Tel.: +81 25 227 2344; Fax: +81 25 227 0793; E-mail: miyashi@bri.niigata-u.ac.jp.

Note: [1] Present address: Department of Neurology, Oita University Faculty of Medicine, Yufu, Japan.

Note: [2] Present address: Department of Medicine for Aging Place Community Health Care/Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Abstract: Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002–0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.

Keywords: Alzheimer's disease, Japanese, rare variants, SNP, TREM2

DOI: 10.3233/JAD-140225

Journal: Journal of Alzheimer's Disease, vol. 41, no. 4, pp. 1031-1038, 2014