Ankara University, Institute of Forensic Sciences, Ankara, Turkey.
Kırşehir Ahi Evran University, Faculty of Science and Art, Department of Molecular Biology and Genetics, Kırşehir, Turkey.
Environ Toxicol Pharmacol. 2022 Oct;95:103979. doi: 10.1016/j.etap.2022.103979. Epub 2022 Sep 26.
The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn't have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.
本研究旨在探讨阿片类使用障碍(OUD)患者中丁丙诺啡(BUP)治疗的遗传贡献,特别关注 BDNF 和 OPRM1 基因。共纳入 113 名对照和 111 名接受舌下 BUP/纳洛酮治疗的 OUD 患者。采用 PCR-FRLP 法检测 OPRM1 A118G 和 BDNF Val66Met 多态性。采用 ELISA 试剂盒检测两组人群的血浆 BDNF 和β-内啡肽水平。采用 LC-MS/MS 法测量血 BUP 水平,并以每日 BUP 剂量(BUP/D)进行标准化。OPRM1 A118G 和 BDNF Val66Met 多态性对 OUD 患者的血浆β-内啡肽和 BDNF 水平均无影响。有趣的是,与对照组相比,OUD 患者的血浆 BDNF 水平显著升高,β-内啡肽水平显著降低(p<0.001)。还发现血浆 BUP/D 与 BDNF 水平呈负相关。首次使用年龄与 OPRM1 A118G 多态性有关。研究结果表明,舌下 BUP/纳洛酮可能会增加 OUD 患者的血浆 BDNF 水平,但可能会降低β-内啡肽水平。似乎 BDNF 水平随 BUP/D 浓度呈下降趋势。