Effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on sublingual buprenorphine metabolism in heroin addicts: An improved PCR-RFLP assay for the detection of rs7662029 polymorphism

AKYÜZLÜ D., Özkan-Kotiloğlu S., BAL C., Yalçın-Şahiner Ş., AVCIOĞLU G., Danışman M.

Environmental Toxicology and Pharmacology, vol.94, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 94
  • Publication Date: 2022
  • Doi Number: 10.1016/j.etap.2022.103902
  • Journal Name: Environmental Toxicology and Pharmacology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Greenfile, MEDLINE, Pollution Abstracts, Veterinary Science Database
  • Keywords: Buprenorphine, Heroin addiction, PCR-RFLP, UGT2B7 variation
  • Ankara Yıldırım Beyazıt University Affiliated: Yes


© 2022 Elsevier B.V.This study aimed to determine the effects of UGT2B7 rs7662029 and rs7439366 polymorphisms on plasma buprenorphine (BUP) concentration and different treatment responses in a sample of 109 patients with opioid use disorder (OUD) treated with sublingual BUP/naloxone. Polymorphisms were analysed by PCR-RFLP. Plasma concentrations of BUP and its metabolite norbuprenorphine were detected by LC–MS/MS. Craving, withdrawal, depression and anxiety were measured by appropriate scales. OUD patients with rs7439366 CC or rs7662029 GG genotypes had significantly lower dose-normalized (BUP/D) and dose/kg-normalized BUP (BUP/D.kg-1) levels than those who were CT or AA carriers. Significant associations between UGT2B7 rs7662029 and increased craving (p = 0.037) and withdrawal symptoms (p = 0.029) were detected. Our findings were pointing to an important role of UGT2B7 in the metabolism of sublingual BUP/naloxone in the heroin addicts for the first time. A novel PCR-RFLP assay was developed for the determination of UGT2B7 rs7662029 polymorphism, based on utilizing novel restriction enzyme.