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舌下给予丁丙诺啡/纳洛酮治疗不受 OPRM1 A118G 和 BDNF Va66Met 多态性的影响,但会改变阿片类物质使用障碍个体的血浆β-内啡肽和 BDNF 水平。

Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms, but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder.

机构信息

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.

出版信息

Environ Toxicol Pharmacol. 2022 Oct;95:103979. doi: 10.1016/j.etap.2022.103979. Epub 2022 Sep 26.

Abstract

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.

摘要

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。

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