Uncoupling protein gene polymorphisms associated with severe periodontitis in Japanese adults

• Project/Area Number: 18K09572
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Niigata University
• Principal Investigator: Sugita Noriko 新潟大学, 医歯学系, 助教 (30313547)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 脱共役タンパク / 歯周炎 / 炎症 / 遺伝子多型 / エネルギー代謝 / ミトコンドリア / UCP / 遺伝型 / サイトカイン / ペリオドンタルメディスン / マクロファージ / エネルギー代謝調節

Outline of Final Research Achievements

Uncoupling proteins (UCP) are mitochondrial membrane transporters which regulate energy expenditure and the metabolism of lipids and carbohydrates. UCP2 is expressed in a broad range of cells including immune cells. UCP3 is expressed in skeletal muscle cells and spleen. We have previously reported associations between the UCP gene polymorphisms and severe periodontitis in postmenopausal women. In vitro study revealed that UCP2 attenuated production of reactive oxygen species and proinflammatory cytokines. In this study, we validated the associations in another Japanese adult population.All outpatients of Sado General Hospital were invited to participate in a cohort study. The final subjects were composed of 115 men and 100 women (mean age 67 years). Edentulous person and participants with missing data were excluded. Adjusted for age, sex, diabetes, body mass index and smoking, the UCP2 rs659366 and the UCP3 rs2075577 were significantly associated with severe periodontitis.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、エネルギー代謝を調節する分子であるUCPが、従来報告されてきた糖尿病や肥満のみならず、歯周炎というヒトの炎症性疾患に関与する可能性をはじめて示唆した。また、骨格筋に多く分布するUCP3の遺伝子多型が有意な関連性を示したことは、歯周炎に対する骨格筋の役割を検討する必要性があることを示している。この成果は歯周炎・糖尿病・肥満のオーダーメイド医療に寄与し、将来、UCPをターゲットとした新しい歯周炎予防・治療法の開発が期待できる。

Research Products

• [Journal Article] Association among periodontitis severity, anti‐agalactosyl immunoglobulin G titer, and the disease activity of rheumatoid arthritis (2021)
  • Author(s): Kaneko Chihiro、Kobayashi Tetsuo、Ito Satoshi、Sugita Noriko、Murasawa Akira、Ishikawa Hajime、Tabeta Koichi
  • Journal Title: Journal of Periodontal Research Volume: 56 Issue: 4 Pages: 702-709
  • DOI: 10.1111/jre.12867
  • Peer Reviewed / Open Access
• [Journal Article] Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island (2020)
  • Author(s): Takamisawa Kei、Sugita Noriko、Komatsu Shigeki、Wakasugi Minako、Yokoseki Akio、Yoshihara Akihiro、Kobayashi Tetsuo、Nakamura Kazutoshi、Onodera Osamu、Momotsu Takeshi、Endo Naoto、Sato Kenji、Narita Ichiei、Yoshie Hiromasa、Tabeta Koichi
  • Journal Title: Heliyon Volume: 6 Issue: 11 Pages: e05531-e05531
  • DOI: 10.1016/j.heliyon.2020.e05531
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study (2020)
  • Author(s): Miyazawa Haruna、Nakajima Takako、Horimizu Makoto、Okuda Kazuhiro、Sugita Noriko、Yamazaki Kyoko、Li Lu、Hayashi-Okada Yoshiko、Arita Takuya、Nishimoto Misa、Nishida Mieko、Genco Robert、Yamazaki Kazuhisa
  • Journal Title: Dentistry Journal Volume: 8 Issue: 4 Pages: 123-123
  • DOI: 10.3390/dj8040123
  • Peer Reviewed / Open Access
• [Journal Article] MAEA rs6815464 polymorphism and periodontitis in postmenopausal Japanese females: A cross-sectional study. (2019)
  • Author(s): Che Y, Sugita N, Yoshihara A, Iwasaki M, Miyazaki H, Nakamura K, Yoshie H.
  • Journal Title: Archives of Oral Biology Volume: 102 Pages: 128-134
  • DOI: 10.1016/j.archoralbio.2019.04.008
  • Peer Reviewed
• [Journal Article] A polymorphism rs6815464 in the macrophage erythroblast attacher gene is associated with low bone mineral density in postmenopausal Japanese women. (2019)
  • Author(s): Che Y, Sugita N, Yoshihara A, Iwasaki M, Miyazaki H, Nakamura K, Yoshie H.
  • Journal Title: Gene Volume: 700 Pages: 1-6
  • DOI: 10.1016/j.gene.2019.03.027
  • Peer Reviewed
• [Journal Article] β 2-Microglobulin and Neutrophil Gelatinase-Associated Lipocalin, Potential Novel Urine Biomarkers in Periodontitis: A Cross-Sectional Study in Japanese. (2019)
  • Author(s): Mayuka Nakajima、Michihiro Hosojima、Koichi Tabeta、Sayuri Miyauchi、Miki Yamada-Hara、Naoki Takahashi、Haruna Miyazawa、Yumi Matsuda-Matsukawa、Keisuke Sato、Noriko Sugita、Yasutaka Komatsu、Tomomi Ishikawa、Kazuhiro Akiishi、Kazuhisa Yamazaki、Kiminori Kato、Akihiko Saito、Hiromasa Yoshie
  • Journal Title: International Journal of Dentistry Volume: 2019 Pages: 1-10
  • DOI: 10.1155/2019/1394678
  • Peer Reviewed / Open Access
• [Journal Article] The number of remaining teeth as a risk indicator of cognitive impairment: A cross-sectional clinical study in Sado Island. (2018)
  • Author(s): Kuroki A, Sugita N, Komatsu S, Wakasugi M, Yokoseki A, Yoshihara A, Kobayashi T, Nakamura K, Momotsu T, Endo N, Sato K, Narita I, Yoshie H
  • Journal Title: Clinical and Experimental Dental Research Volume: 4 Issue: 6 Pages: 291-296
  • DOI: 10.1002/cre2.147
  • Peer Reviewed / Open Access
• [Presentation] Uncoupling protein 2 gene polymorphism associated with severe periodontitis in Japanese adults (2022)
  • Author(s): N. Sugita, S. Komatsu, H. Lyu, A. Yoshihara, T. Kobayashi, K. Tabeta
  • Organizer: EuroPerio10
  • Int'l Joint Research
• [Presentation] 間接リウマチ患者におけるPISA、RA活動度および好中球細胞外トラップ血清レベルの関連性 (2019)
  • Author(s): 金子千尋、小林哲夫、杉田典子、吉江弘正、村澤章、中園清、伊藤聡
  • Organizer: 第62回春季日本歯周病学会学術大会
• [Presentation] 血清抗Porphyromonas gingivalis IgG抗体価と肝機能マーカー値の関連性 新潟県佐渡市における横断研究 (2019)
  • Author(s): 高見澤圭、杉田典子、葭原明弘、小林哲夫、吉江弘正、多部田康一
  • Organizer: 第62回秋季日本歯周病学会学術大会
• [Presentation] Uncoupling protein 2 attenuates production of reactive oxygen species and interleukin-8 in THP-1 cells stimulated with Porphyromonas gingivalis-derived lipopolysaccharide. (2018)
  • Author(s): Sugita N, Takahashi N, Che Y, Takamisawa K, Yoshie H.
  • Organizer: EUROPERIO 9
  • Int'l Joint Research
• [Presentation] The effect of Gli-similar 3 gene polymorphism on the relationship between periodontitis and renal function in postmenopausal Japanese women. (2018)
  • Author(s): Takamisawa K, Sugita N, Yoshihara A, Iwasaki M, Che Y, Kuroki A, Miyazaki H, Nakamura K, Yoshie H.
  • Organizer: EUROPERIO 9
  • Int'l Joint Research
• [Presentation] Associations between cognitive impairment and number of teeth classified in small groups: a cross-sectional clinical study in Sado Island. (2018)
  • Author(s): Kuroki A, Sugita N, Kobayashi T, Yoshihara A, Nakamura K, Yoshie H.
  • Organizer: EUROPERIO 9
  • Int'l Joint Research
• [Presentation] Expression and function of macrophage erythroblast attacher in THP-1 cells and human periodontal ligament fibroblasts stimulated with Porphyromonas gingivalis derived lipopolysaccharide. (2018)
  • Author(s): Che Y, Sugita N, Takahashi N, Takamisawa K, Yoshie H.
  • Organizer: EUROPERIO 9
  • Int'l Joint Research