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.

Kaya-Akyüzlü D., Özkan-Kotiloğlu S., Bal C., Yalçın-Şahiner Ş., Avcıoğlu G., Danışman M.

Environmental toxicology and pharmacology, cilt.94, ss.103902, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 94
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.etap.2022.103902
  • Dergi Adı: Environmental toxicology and pharmacology
  • Derginin Tarandığı İndeksler: 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
  • Sayfa Sayıları: ss.103902
  • Anahtar Kelimeler: UGT2B7 variation, Heroin addiction, Buprenorphine, PCR-RFLP, GLUCURONOSYLTRANSFERASE 2B7 UGT2B7, GENETIC POLYMORPHISMS, PLASMA-CONCENTRATIONS, VALPROIC ACID, GLUCURONIDATION, VARIANTS, MORPHINE, UGT1A9, ASSOCIATION, ANDROGENS
  • Ankara Üniversitesi Adresli: Evet

Özet

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.