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

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-...

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Published in:Environmental toxicology and pharmacology 2022-08, Vol.94, p.103902-103902, Article 103902
Main Authors: Kaya-Akyüzlü, Dilek, Özkan-Kotiloğlu, Selin, Bal, Ceylan, Yalçın-Şahiner, Şafak, Avcıoğlu, Gamze, Danışman, Mustafa
Format: Article
Language:English
Subjects:
Buprenorphine
Heroin addiction
PCR-RFLP
UGT2B7 variation
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Summary: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. •The UGT2B7 rs7439366 and rs7662029 SNPs affected sublingual BUP metabolism.•Heroin addicts with the UGT2B7 rs7439366 CT had higher BUP/D level compared to CC.•Heroin addicts with the UGT2B7 rs7662029 AA had higher BUP/D level compared to GG.•The UGT2B7 rs7662029 polymorphism had an effect on craving and withdrawal symptoms.•A novel PCR-RFLP assay was developed for the determination of UGT2B7 rs7662029 SNP.
ISSN:1382-6689
1872-7077
DOI:10.1016/j.etap.2022.103902