103學年度第二學期專題討論統計學術演講公告
統計碩士學位學程將於104年3月3日(星期二)舉辦統計學術演講，邀請到中央研究院統計科學研究所楊欣洲副研究員蒞臨演講，
講題：Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients
講員：楊欣洲 副研究員 中央研究院統計科學研究所
時間：2015年3月3日星期二 下午 3：30 ~ 5：30
地點：臺灣大學博雅教學館409教室
費用：免費
名額：24位
摘要：
Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10-8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomers. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomers. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration, in which two significant haplotypes on CYP2B6 accounted for 10.72% of the variation. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.
This is a joint work with Shih-Kai Chu, Hsiang-Wei Kuo, Sheng-Chang Wang, Sheng-Wen Liu, Ing-Kang Ho, and Yu-Li Liu
歡迎對於此議題有興趣的師生同仁參加。
聯絡人：張仲凱
聯絡方式：E-mail：ntustat@ntu.edu.tw
TEL：(02) 3366-1481 FAX：(02) 3366-1482