A modeling and simulation approach to determining the risk for diabetes incorporating the genetic polymorphisms

• Project/Area Number: 15K18925
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Oniki Kentaro 熊本大学, 大学院生命科学研究部(薬), 助教 (00613407)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: NAFLD / 糖尿病 / DsbA-L / NONMEM / 統合失調症 / 肥満 / ALDH2 / 個別化予防 / 非アルコール性脂肪性肝疾患 / 遺伝子多型 / PNPLA3 / 遺伝子変異

Outline of Final Research Achievements

・We established a BMI-based prediction model for non-alcoholic fatty liver disease (NAFLD) using a NONMEM program.The determination of the high-risk group for NAFLD based on a population NAFLD model may be useful for individualized health promotion.
・We showed that the disulfide bond-forming oxidoreductase A-Like protein(DsbA-L) rs1917760 polymorphism leads to a decreased expression of DsbA-L mRNA in PBMCs from Schizophrenia(SCZ) patients, resulting in an increased risk for being overweight in SCZ male patients. Therefore, the DsbA-L T/T genotype may be a novel risk factor for predicting an overweight status in SCZ male patients.
・We showed that the inactive aldehyde dehydrogenase (ALDH2)*2 allele may potentially be a novel risk factor for NAFLD in relation to an elevated gamma-glutamyl transferase level.

Research Products

• [Journal Article] Predictive factors for effectiveness and safety of enoxaparin for total knee arthroplasty in aged Japanese patients: a retrospective review (2017)
  • Author(s): Sonoda A, Kondo Y, Tsuneyoshi Y, Iwashita Y, Nakao S, Ishida K, Oniki K, Saruwatari J, Irie T, Ishitsuka Y.
  • Journal Title: Journal of Pharmaceutical Health Care and Sciences Volume: 3 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s40780-017-0075-x
  • Peer Reviewed / Open Access
• [Journal Article] Common variants of HNF1A gene are associated with diabetic retinopathy and poor glycemic control in normal-weight Japanese subjects with type 2 diabetes mellitus. (2017)
  • Author(s): Morita K, Saruwatari J, Tanaka T, Oniki K, Kajiwara A, Miyazaki H, Yoshida A, Jinnouchi H, Nakagawa K.
  • Journal Title: J Diabetes Complications. Volume: 31 Issue: 2 Pages: 483-488
  • DOI: 10.1016/j.jdiacomp.2016.06.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina. (2016)
  • Author(s): Akasaka T, Sueta D, Arima Y, Tabata N, Takashio S, Izumiya Y, Yamamoto E, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Kajiwara A, Morita K, Oniki K, Saruwatari J, Nakagawa K, Ogata Y, Matsui K, Hokimoto S.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 311 Issue: 6 Pages: H1409-H1415
  • DOI: 10.1152/ajpheart.00473.2016
  • Peer Reviewed
• [Journal Article] Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis. (2016)
  • Author(s): Nishimura M, Ueda M, Saruwatari J, Nakashima H, Ogusu N, Aoki A, Tsuchimine S, Matsuda K, Iwashita K, Ono T, Oniki K, Shimoda K, Yasui-Furukori N.
  • Journal Title: Pharmacogenet Genomics. Volume: 26 Issue: 9 Pages: 403-13
  • DOI: 10.1097/fpc.0000000000000228
  • Peer Reviewed
• [Journal Article] Gender Differences in the Impact of CYP2C19 Polymorphisms and Low-Grade Inflammation on Coronary Microvascular Disorder. (2016)
  • Author(s): Akasaka T, Hokimoto S, Sueta D, Tabata N, Sakamoto K, Yamamoto E, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Kajiwara A, Morita K, Oniki K, Saruwatari J, Nakagawa K, Ogata Y, Ogawa H.
  • Journal Title: Am. J. Physiol. Heart Circ. Volume: - Issue: 11 Pages: H1494-H1500
  • DOI: 10.1152/ajpheart.00911.2015
  • Peer Reviewed
• [Journal Article] Helicobacter Pylori-seropositivity along with genetic and environmental factors predicts clinical outcome after acute coronary syndrome. (2016)
  • Author(s): Tabata N, Hokimoto S, Akasaka T, Sueta D, Arima Y, Sakamoto K, Yamamoto E, Izumiya Y, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Morita K, Oniki K, Saruwatari J, Nakagawa K, Ogawa H.
  • Journal Title: Int J Cardiol. Volume: 212 Pages: 54-56
  • DOI: 10.1016/j.ijcard.2016.03.034
  • Peer Reviewed / Open Access
• [Journal Article] The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease (2016)
  • Author(s): Oniki K, Morita K, Watanabe T, Kajiwara A, Otake K, Nakagawa K, Sasaki Y, Ogata Y, Saruwatari J.
  • Journal Title: Nutr Diabetes. Volume: 6 Issue: 5 Pages: e210-e210
  • DOI: 10.1038/nutd.2016.17
  • Peer Reviewed / Open Access
• [Journal Article] Helicobacter pylori Seropositivity in Patients with Interleukin-1 Polymorphisms Is Significantly Associated with ST-Segment Elevation Myocardial Infarction. (2016)
  • Author(s): Tabata N, Sueta D, Akasaka T, Arima Y, Sakamoto K, Yamamoto E, Izumiya Y, Yamamuro M, Tsujita K, Kojima S, Kaikita K, Morita K, Oniki K, Saruwatari J, Nakagawa K, Hokimoto S.
  • Journal Title: PLoS One. Volume: 11 Issue: 11 Pages: e0166240-e0166240
  • DOI: 10.1371/journal.pone.0166240
  • Peer Reviewed / Open Access
• [Journal Article] Prescription of triazolam for the elderly in Japan: A sub-analysis of the drug event monitoring project by the Japan Pharmaceutical Association. (2016)
  • Author(s): Kajiwara A, Ishizuka T, Yamamura M, Murase M, Koda H, Hirota S, Morita K, Oniki K, Saruwatari J, Nakagawa K.
  • Journal Title: Clin Neuropsychopharmacol Ther. Volume: 7 Pages: 48-53
  • NAID: 130005279585
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 抗てんかん薬のTDMと有効血中濃度域の考え方 (2016)
  • Author(s): 猿渡淳二、鬼木健太郎、平田憲史郎、石津棟暎．
  • Journal Title: 臨床化学 Volume: 45 Pages: 233-239
• [Journal Article] 検査からみる神経疾患 抗てんかん薬のファルマコゲノミクス検査 (2016)
  • Author(s): 鬼木健太郎、猿渡淳二．
  • Journal Title: Clinical Neuroscience Volume: 34 Pages: 1170-1171
• [Journal Article] Safety analysis of zolpidem in elderly subjects 80 years of age or older: Adverse event monitoring in Japanese subjects. (2016)
  • Author(s): Kajiwara A, Yamamura M, Murase M, Koda H, Hirota S, Ishizuka T, Morita K, Oniki K, Saruwatari J & Nakagawa K.
  • Journal Title: Aging & mental health Volume: 印刷中 Issue: 6 Pages: 611-615
  • DOI: 10.1080/13607863.2015.1031640
  • Peer Reviewed / Open Access
• [Journal Article] Sex Differences in the Renal Function Decline of Patients with Type 2 Diabetes. (2016)
  • Author(s): Kajiwara A, Kita A, Saruwatari J, Miyazaki H, Kawata Y, Morita K, Oniki K, Yoshida A, Jinnouchi H, Nakagawa K.
  • Journal Title: J Diabetes Res. Volume: - Pages: 4626382-4626382
  • DOI: 10.1155/2016/4626382
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Effect of <i>Yokukansan</i>, a Traditional Herbal Preparation Used for the Behavioral and Psychological Symptoms of Dementia, on the Drug–Metabolizing Enzyme Activities in Healthy Male Volunteers (2016)
  • Author(s): Soraoka H, Oniki K, Matsuda K, Ono T, Taharazako K, Uchiyashiki Y, Kamihashi R, Kita A, Takashima A, Nakagawa K, Yasui-Furukori N, Kadowaki D, Miyata K, Saruwatari J.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 9 Pages: 1468-1474
  • DOI: 10.1248/bpb.b16-00248
  • NAID: 130005262324
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access
• [Journal Article] The longitudinal effect of the aldehyde dehydrogenase 2 *2 allele on the risk for non-alcoholic fatty liver disease. (2016)
  • Author(s): Oniki K, Morita K, Watanabe T, Kajiwara A, Otake K, Nakagawa K, Sasaki Y, Ogata Y, Saruwatari J.
  • Journal Title: Nutr & Diabetes Volume: in press
  • Open Access / Acknowledgement Compliant
• [Journal Article] Glutathione S-transferase K1 genotype and overweight status in schizophrenia patients: A pilot study. (2016)
  • Author(s): Oniki K, Kamihashi R, Tomita T, Ishioka M, Yoshimori Y, Osaki N, Tsuchimine S, Sugawara N, Kajiwara A, Morita K, Miyata K, Otake K, Nakagawa K, Ogata Y, Saruwatari J, Yasui-Furukori N.
  • Journal Title: Psychiatry Res. Volume: 239 Pages: 190-195
  • DOI: 10.1016/j.psychres.2016.03.025
  • Peer Reviewed / Open Access
• [Journal Article] Determination of the Optimal Concentration of Valproic Acid in Patients with Epilepsy: A Population Pharmacokinetic-Pharmacodynamic Analysis. (2015)
  • Author(s): Nakashima H, Oniki K, Nishimura M, Ogusu N, Shimomasuda M, Ono T, Matsuda K, Yasui-Furukori N, Nakagawa K, Ishitsu T, Saruwatari J.
  • Journal Title: PLoS One Volume: 10 Issue: 10 Pages: e0141266-e0141266
  • DOI: 10.1371/journal.pone.0141266
  • Peer Reviewed / Open Access
• [Journal Article] Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects. (2015)
  • Author(s): Oniki K, Saruwatari J, Izuka T, Kajiwara A, Morita K, Sakata M, Otake K, Ogata Y, Nakagawa K.
  • Journal Title: PLoS ONE Volume: 10 Issue: 7 Pages: e0132640-e0132640
  • DOI: 10.1371/journal.pone.0132640
  • Peer Reviewed / Open Access
• [Presentation] BMIの個体間変動に基づくNAFLD予測モデルの構築とその予防的応用に関する検討 (2017)
  • Author(s): 鬼木健太郎、工藤未来、小野達昌、松田和樹、武藤奈瑠美、居塚智子、渡邊丈久、大竹宏治、緒方康博、猿渡淳二
  • Organizer: 第16回分子予防環境医学研究会大会
  • Place of Presentation: 熊本
  • Year and Date: 2017-02-03
• [Presentation] BMIの個体間変動に基づくNAFLDリスクの予測モデルの構築 (2016)
  • Author(s): 鬼木健太郎、工藤未来、小野達昌、武藤奈瑠美、渡邊丈久、猿渡淳二
  • Organizer: 第108回日本消化器病学会九州支部例会・第102 回日本消化器内視鏡学会九州支部例会
  • Place of Presentation: 熊本
  • Year and Date: 2016-11-25
  • Invited
• [Presentation] 抗てんかん薬バルプロ酸の治療効果に関する母集団薬物動態―薬力学解析 (2016)
  • Author(s): 鬼木健太郎、中嶋洋生、西村美紀、大楠直樹、小野達昌、松田 和樹、古郡規雄、石津棟暎、猿渡淳二
  • Organizer: 医療薬学フォーラム2016／第24回クリニカルファーマシーシンポジウム
  • Place of Presentation: 滋賀
  • Year and Date: 2016-06-25
• [Presentation] Aldehyde dehydrogenase 2 遺伝子変異が非アルコール性脂肪性肝疾患に及ぼす影響 (2016)
  • Author(s): 鬼木健太郎、渡邊丈久、武藤奈瑠美、佐々木裕、猿渡淳二
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 幕張
  • Year and Date: 2016-05-19
• [Presentation] Disulfide-bond A oxidoreductase-like protein遺伝子変異と統合失調症患者の肥満との関係 (2016)
  • Author(s): 鬼木健太郎、大﨑夏海、上橋諒子、冨田哲、石岡雅道、土嶺章子、菅原典夫、大竹宏治、緒方康博、古郡規雄、猿渡淳二
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 非アルコール性脂肪性肝疾患予防のための非肥満者におけるPNPLA3遺伝子変異の意義 (2015)
  • Author(s): 鬼木健太郎，武藤奈瑠美，守田和憲，居塚智子，梶原彩文，坂田美咲，北愛矢菜，熊谷直樹，大竹宏治，緒方康博，中川和子，猿渡淳二
  • Organizer: 第25回日本医療薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2015-11-21