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Research Papers:

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

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 and Masashi Tanaka

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Oncotarget. 2017; 8:38950-38961. https://doi.org/10.18632/oncotarget.17159

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Abstract

Yoshiji Yamada1,2, Jun Sakuma2,3,4, Ichiro Takeuchi2,4,5, Yoshiki Yasukochi1,2, Kimihiko Kato1,6, Mitsutoshi Oguri1,7, Tetsuo Fujimaki8, Hideki Horibe9, Masaaki Muramatsu10, Motoji Sawabe11, Yoshinori Fujiwara12, Yu Taniguchi12, Shuichi Obuchi13, Hisashi Kawai13, Shoji Shinkai14, Seijiro Mori15, Tomio Arai16, Masashi Tanaka17

1Department of Human Functional Genomics, Advanced Science Research Promotion Center, Mie University, Tsu, Japan

2CREST, Japan Science and Technology Agency, Kawaguchi, Japan

3Computer Science Department, College of Information Science, University of Tsukuba, Tsukuba, Japan

4RIKEN Center for Advanced Intelligence Project, Tokyo, Japan

5Department of Computer Science, Nagoya Institute of Technology, Nagoya, Japan

6Department of Internal Medicine, Meitoh Hospital, Nagoya, Japan

7Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Japan

8Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Japan

9Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan

10Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

11Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan

12Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

13Research Team for Promoting Support System for Home Care, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

14Research Team for Social Participation and Health Promotion, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

15Center for Promotion of Clinical Investigation, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

16Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

17Department 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.


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