Association study of genetic polymorphisms in ABCB1, CYP2B6, CYP2D6 genes and efficacy dosage for methadone therapy in Han heroin dependence patients

• Main Authors: Ju-Ting Lu, 呂如婷
• Other Authors: Shin-Hsin Wu
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/64877175118359429690

碩士 === 慈濟大學 === 生物化學碩士班 === 104 === Opioids dependence is one of the most serious problems affecting social norms and public health system. Methadone Maintenance Therapy (MMT) is now widely used to treat heroin dependence with high efficacy. Methadone is a synthetic opioid anesthetic, past studies showed that gene polymorphism and individual’s differences may affect the pharmacodynamics of Methadone, which is majorly metabolized by Cytochrome P450 and P-glycoprotein. Studies also showed that genetic variations of CYP450 CYP2B6, G516T and A785G enzyme are related to Methadone blood concentration, and CYP2D6*10, with high variations in Asians, plays a major role in Methadone metabolism. Besides, ABCB1 C1236T, G2677T and C3435T gene variants of P-glycoprotein are confirmed to be related to effectiveness of MMT. This study is to explore the relationship between CYP450 genetic polymorphism (ABCB1, CYP2B6, ＆CYP2D6*10) and effective dosage of Methadone. The study subjects were heroin dependence outpatient treated with MMT in Lotung Poh-Ai and General Keelung Hospitals in northern Taiwan. The study protocol was approval by the Ethics Committees of Cathy Hospital. From January 2015 to September 2015, a total of 100 (82 men and 18 women, the average age is 42.53±6.65 years respectively,) heroin dependence patients were enrolled. Characteristics including daily Methadone dosage, BMI index, and other clinical data were collected; gene extraction from oral mucosa and was analyzed via Real-time PCR. Our study finds that the average Methadone dosage in different sex, BMI index, ABCB1 2677GG and CYP2B6 516GG variations is statistically significant. Male(p＜0.009), BMI＞25(p＜0.007), and CYP2B6 516GG homozygote are related to higher average Methadone dosage(p＜0.02), while ABCB1 2677GG homozygote is related to lower dosage(p＜0.05). Multiple linear regression is done to examine the relationship between variants above and average Methadone dosage, and it can predict more than 30% of effective Methadone dosage in our study objects. The future in-depth study to explore interactions between variants above and effective MMT dosage is warrant. This study outcome should be helpful to precisely dosing MMT for Taiwan Heroin dependence patients in the future. Key words: Methadone Maintenance Therapy (MMT), Genetic polymorphism , Pharmacodynamics.