Development of the personalized medicine for pulmonary arterial hypertension by the pharmacogenomic approach

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460213
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Emoto Noriaki 神戸薬科大学, 薬学部, 教授 (30294218)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肺高血圧症 / 個別化医療 / ゲノム / エンドセリン受容体拮抗薬 / 遺伝子多型

Outline of Final Research Achievements

The purpose of this study was to create the clinical database for pulmonary hypertension and to identify genomic biomarkers that predict effectiveness and adverse effects of disease targeting drugs. An exploratory analysis of 1,936 SNPs in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using DMET chips, was performed. We extracted 16 SNPs using Jonckheere-Terpstra trend test, and by using multiplex logistic analysis, we identified two SNPs in two genes significantly associated with bosentan-induced liver injury. We conducted ROC analysis by using 2 SNPs and 2 items of non-genetic factor, and we constructed predictive model for bosentan-induced liver injury. These results may provide not only a way to personalized medicine for PAH but also novel mechanistic insights on drug-induced liver dysfunction.

Free Research Field

臨床薬理学