Oncotarget

Research Papers:

Identification of C21orf59 and ATG2A as novel determinants of renal function-related traits 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

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:45259-45273. https://doi.org/10.18632/oncotarget.16696

Metrics: PDF 1464 views  |   HTML 2382 views  |   ?  


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: [email protected]

Keywords: chronic kidney disease, hyperuricemia, glomerular filtration rate, serum uric acid, exome-wide association study

Received: February 12, 2017    Accepted: March 08, 2017    Published: March 30, 2017

ABSTRACT

We have performed exome-wide association studies to identify genetic variants that influence renal function-related traits or confer susceptibility to chronic kidney disease or hyperuricemia in Japanese. Exome-wide association studies for estimated glomerular filtration rate and the serum concentration of creatinine were performed with 12,565 individuals, that for the serum concentration of uric acid with 9934 individuals, and those for chronic kidney disease or hyperuricemia with 5161 individuals (3270 cases, 1891 controls) or 11,686 individuals (2045 cases, 9641 controls), respectively. The relation of genotypes of single nucleotide polymorphisms to estimated glomerular filtration rate or the serum concentrations of creatinine or uric acid was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to chronic kidney disease or hyperuricemia was examined with Fisher’s exact test. The exome-wide association studies revealed that 25, seven, and six single nucleotide polymorphisms were significantly (P <1.21 × 10–6) associated with estimated glomerular filtration rate or the serum concentrations of creatinine or uric acid, respectively, and that 49 and 35 polymorphisms were significantly associated with chronic kidney disease or hyperuricemia, respectively. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that four and three single nucleotide polymorphisms were related (P < 0.05) to chronic kidney disease or hyperuricemia, respectively. Among polymorphisms identified in the present study, rs76974938 [C/T (D67N)] of C21orf59 and rs188780113 [G/A (R478C)] of ATG2A may be novel determinants of estimated glomerular filtration rate and chronic kidney disease or of the serum concentration of uric acid, respectively.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 16696