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Identification of eight genetic variants as novel determinants of dyslipidemia in Japanese by exome-wide association studies

2017; Impact Journals LLC; Volume: 8; Issue: 24 Linguagem: Inglês

10.18632/oncotarget.17159

1949-2553

Yoshiji Yamada, Jun Sakuma, Ichiro Takeuchi, Yoshiki Yasukochi, Kimihiko Kato, Mitsutoshi Oguri, Tetsuo Fujimaki, Hideki Horibe, Masaaki Muramatsu, Motoji Sawabe, Yoshinori Fujiwara, Yu Taniguchi, Shuichi Obuchi, Hisashi Kawai, Shoji Shinkai, Seijiro Mori, Tomio Arai, Masashi Tanaka,

Peroxisome Proliferator-Activated Receptors

// Yoshiji Yamada 1, 2 , Jun Sakuma 2, 3, 4 , Ichiro Takeuchi 2, 4, 5 , Yoshiki Yasukochi 1, 2 , Kimihiko Kato 1, 6 , Mitsutoshi Oguri 1, 7 , Tetsuo Fujimaki 8 , Hideki Horibe 9 , Masaaki Muramatsu 10 , Motoji Sawabe 11 , Yoshinori Fujiwara 12 , Yu Taniguchi 12 , Shuichi Obuchi 13 , Hisashi Kawai 13 , Shoji Shinkai 14 , Seijiro Mori 15 , Tomio Arai 16 , Masashi Tanaka 17 1 Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan 2 CREST, Japan Science and Technology Agency, Kawaguchi, Japan 3 Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba, Japan 4 RIKEN Center for Advanced Intelligence Project, Tokyo, Japan 5 Department of Computer Science, Nagoya Institute of Technology, Nagoya, Japan 6 Department of Internal Medicine, Meitoh Hospital, Nagoya, Japan 7 Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Japan 8 Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan 9 Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan 10 Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan 11 Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan 12 Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 13 Research Team for Promoting Support System for Home Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 14 Research Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan 15 Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan 16 Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan 17 Department of Clinical Laboratory, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan Correspondence to: Yoshiji Yamada, email: yamada@gene.mie-u.ac.jp Keywords: triglyceride, HDL-cholesterol, LDL-cholesterol, dyslipidemia, exome-wide association study Received: March 03, 2017 Accepted: April 04, 2017 Published: April 17, 2017 ABSTRACT We have performed exome-wide association studies to identify single nucleotide polymorphisms that influence serum concentrations of triglycerides, high density lipoprotein (HDL)–cholesterol, or low density lipoprotein (LDL)–cholesterol or confer susceptibility to hypertriglyceridemia, hypo–HDL-cholesterolemia, or hyper–LDL-cholesterolemia in Japanese. Exome-wide association studies for serum triglycerides (13,414 subjects), HDL-cholesterol (14,119 subjects), LDL-cholesterol (13,577 subjects), hypertriglyceridemia (4742 cases, 8672 controls), hypo–HDL-cholesterolemia (2646 cases, 11,473 controls), and hyper–LDL-cholesterolemia (4489 cases, 9088 controls) were performed with HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. Twenty-four, 69, or 32 loci were significantly ( P < 1.21 × 10 –6 ) associated with serum triglycerides, HDL-cholesterol, or LDL-cholesterol, respectively, with 13, 16, or 9 of these loci having previously been associated with triglyceride-, HDL-cholesterol–, or LDL-cholesterol–related traits, respectively. Two single nucleotide polymorphisms (rs10790162, rs7350481) were significantly related to both serum triglycerides and hypertriglyceridemia; three polymorphisms (rs146515657, rs147317864, rs12229654) were significantly related to both serum HDL-cholesterol and hypo–HDL-cholesterolemia; and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) were significantly related to both serum LDL-cholesterol and hyper–LDL-cholesterolemia. Among polymorphisms identified in the present study, two polymorphisms (rs146515657, rs147317864) may be novel determinants of hypo–HDL-cholesterolemia, and six polymorphisms (rs2853969, rs7771335, rs2071653, rs2269704, rs2269703, rs2269702) may be new determinants of hyper–LDL-cholesterolemia. In addition, 12, 61, 23, or 3 polymorphisms may be new determinants of the serum triglyceride, HDL-cholesterol, or LDL-cholesterol concentrations or of hyper–LDL-cholesterolemia, respectively.