title: A possible role for HLA-DRB1*04:06 in statin-related myopathy in Japanese patients.
abstract: Statin-related myopathy (SRM) is a clinically important adverse reaction. Recent pharmacogenetic research, mainly in non-Asian populations, have indicated clinical relevance of some of genetic biomarkers to SRM, but predictive markers for SRM in Asian populations including Japanese has not yet been established. This study was aimed to identify clinically important genetic markers associated with SRM in Japanese patients. Allele frequencies of the three reported candidate markers - SLCO1B1 rs4149056, RYR2 rs2819742, and GATM rs9806699 - and carrier frequencies of HLA types were compared between patients with SRM patients (n = 52) and healthy Japanese subjects (n = 2878 or 86 (for rs9806699) as controls). No significant association of RYR2, SLCO1B1, and GATM variants with SRM were observed in our Japanese patients, but a significant association was detected for HLA-DRB1*04:06 with SRM (odds ratio: 3.19; 95% confidence interval: 1.53-6.66). This study suggested that HLA-DRB1*04:06 might be associated with SRM onset in a Japanese population. Further studies are required to validate these results.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. Electronic address: sai@nihs.go.jp.
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kajinami
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Akao
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Iwadare
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sato-Ishida
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa 920-0293, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanimoto
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamano
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Hirata
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
authors.affiliation: Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 2-24, Shinkura-cho, Tokushima 770-8501, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yagi
authors.affiliation: Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 2-24, Shinkura-cho, Tokushima 770-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.affiliation: Department of Cardiovascular Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 2-24, Shinkura-cho, Tokushima 770-8501, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kindai University Faculty of Medicine, 377-2, Ono-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kindai University Faculty of Medicine, 377-2, Ono-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Department of Cardiovascular Medicine, Saga University, 1 Honjo-machi, Saga 840-8502, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Shiraki
authors.affiliation: Department of Cardiovascular Medicine, Saga University, 1 Honjo-machi, Saga 840-8502, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Oyama
authors.affiliation: Department of Cardiovascular Medicine, Saga University, 1 Honjo-machi, Saga 840-8502, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugamura
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuzawa
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Imatoh
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hasegawa
authors.affiliation: Japanese Pharmacogenomics Data Science Consortium, 4-11-6 Kuramae, Taito-ku, Tokyo 111-0051, Japan.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000368:Aged; D005260:Female; D005819:Genetic Markers; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced / Q000235:genetics*; D063806:Myalgia / Q000139:chemically induced / Q000235:genetics; D009220:Myositis / Q000139:chemically induced / Q000235:genetics; D012206:Rhabdomyolysis / Q000139:chemically induced / Q000235:genetics
chemical_list: D005819:Genetic Markers; D059811:HLA-DRB1 Chains; C518670:HLA-DRB1*04:06 antigen; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Genetic polymorphism; HLA; Myopathy; Rhabdomyolysis; Statin