著者

Mineko Tsukamoto Asahi Hishida Takashi Tamura Mako Nagayoshi Rieko Okada Yoko Kubo Yasufumi Kato Nobuyuki Hamajima Yuichiro Nishida Chisato Shimanoe Rie Ibusuki Kenichi Shibuya Naoyuki Takashima Yasuyuki Nakamura Miho Kusakabe Yohko Nakamura Yuriko N. Koyanagi Isao Oze Takeshi Nishiyama Sadao Suzuki Isao Watanabe Daisuke Matsui Jun Otonari Hiroaki Ikezaki Sakurako Katsuura-Kamano Kokichi Arisawa Kiyonori Kuriki Masahiro Nakatochi Yukihide Momozawa Kenji Takeuchi Kenji Wakai Keitaro Matsuo

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20220341, (Released:2023-07-29)

参考文献数

72

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Background: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese.Methods: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed.Results: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048).Conclusions: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.

著者

Ryosuke Fujii Hiroya Yamada Eiji Munetsuna Mirai Yamazaki Koji Ohashi Hiroaki Ishikawa Keisuke Maeda Chiharu Hagiwara Yoshitaka Ando Shuji Hashimoto Nobuyuki Hamajima Koji Suzuki

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

vol.30, no.4, pp.177-182, 2020-04-05 (Released:2020-04-05)

参考文献数

63

被引用文献数

13

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Background: MicroRNAs (miRNAs) play crucial roles in the development of various diseases, including chronic kidney disease (CKD). Although previous studies in clinically severe patients have investigated associations between CKD and miRNAs, with particular attention on renal fibrosis, relationships in a general population have yet to be established. The aim of this study was to examine the relationship between expression level of circulating miRNAs and CKD in a middle-aged Japanese population.Methods: A final total of 513 individuals (216 men and 297 women) who participated in the health check-up program in 2012 were included in our analysis. Quantitative real-time polymerase chain reaction was used to determine expression levels of 22 miRNAs. Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine level, sex, and age. Participants with eGFR <60 mL/min/1.73 m2 were defined as having CKD.Results: Three different miRNAs (miR-17, miR-21, and miR-150) showed significant correlations with eGFR after Bonferroni correction and were selected for further analyses. Expression levels of miR-17, miR-21, and miR-150 miRNAs were positively associated with eGFR after adjusting for potential confounders (P = 0.004, 0.002, and 0.004, respectively). Logistic regression analyses showed significantly lower odds ratios for CKD (eGFR <60 mL/min/1.73 m2) in the highest tertile of all three miRNAs (miR-17, miR-21, and miR-150) compared with the lowest tertile (P = 0.003, 0.01, and 0.02, respectively).Conclusions: We found that three circulating miRNAs were significantly associated with CKD in a general Japanese population, which suggested that these miRNAs may be biomarkers for CKD among general adults.