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Research Papers:

Identification of polymorphisms in 12q24.1, ACAD10, and BRAP as novel genetic determinants of blood pressure 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; 8:43068-43079. https://doi.org/10.18632/oncotarget.17474

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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 and 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: hypertension, blood pressure, genetics, exome-wide association study, polymorphism

Received: March 19, 2017     Accepted: April 05, 2017     Published: April 27, 2017

ABSTRACT

We performed exome-wide association studies to identify genetic variants that influence systolic or diastolic blood pressure or confer susceptibility to hypertension in Japanese. The exome-wide association studies were performed with the use of Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays and with 14,678 subjects, including 8215 individuals with hypertension and 6463 controls. The relation of genotypes of 41,843 single nucleotide polymorphisms to systolic or diastolic blood pressure was examined by linear regression analysis. After Bonferroni’s correction, 44 and eight polymorphisms were significantly (P < 1.19 × 10–6) associated with systolic or diastolic blood pressure, respectively, with six polymorphisms (rs12229654, rs671, rs11066015, rs2074356, rs3782886, rs11066280) being associated with both systolic and diastolic blood pressure. Examination of the relation of allele frequencies to hypertension with Fisher’s exact test revealed that 100 of the 41,843 single nucleotide polymorphisms were significantly (P < 1.19 × 10–6) associated with hypertension. Subsequent multivariable logistic regression analysis with adjustment for age and sex showed that five polymorphisms (rs150854849, rs202069030, rs139012426, rs12229654, rs76974938) were significantly (P < 1.25 × 10–4) associated with hypertension. The polymorphism rs12229654 was thus associated with both systolic and diastolic blood pressure and with hypertension. Six polymorphisms (rs12229654 at 12q24.1, rs671 of ALDH2, rs11066015 of ACAD10, rs2074356 and rs11066280 of HECTD4, and rs3782886 of BRAP) were found to be associated with both systolic and diastolic blood pressure, with those at 12q24.1 or in ACAD10 or BRAP being novel determinants of blood pressure in Japanese.


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