Vpliv variabilnosti gena OPRM1 za opioidni receptor mu 1 na izid zdravljenja s tramadolom

Vidic, Zala (author), Dolžan, Vita (mentor)

Opioidni receptor mu, ki ga kodira OPRM1, je ključen za protibolečinsko delovanje opioidnih zdravil. Je tarča tramadola, ki spada med centralno delujoče opioidne analgetike za lajšanje zmernih do močnih akutnih in kroničnih bolečin. Genetski polimorfizmi OPRM1 in genov za miRNA lahko zaradi spremenjenega izražanja ali občutljivosti receptorja vplivajo na izid zdravljenja s tramadolom. V raziskavi smo želeli z genotipizacijo s kvantitativno alelno specifično verižno reakcijo s polimerazo določiti frekvence polimorfizmov OPRM1 rs1799971, OPRM1 rs677830, MIR23B 1011784 in MIR107 rs2296616 v skupini preiskovank po operaciji raka dojke in ovrednotiti njihov vpliv na jakost akutne bolečine in prisotnost neželenih učinkov ter kronične in nevropatske bolečine. Nosilke vsaj enega polimorfnega alela MIR107 rs2296616 A so imele manjše tveganje za pojav slabosti v tretjem tednu zdravljenja, preiskovanke z genotipom MIR23B 1011784 GG pa večje tveganje za pojav slabosti v četrtem tednu. Večje tveganje za pojav zaprtosti kadarkoli v prvem mesecu smo potrdili pri nosilkah vsaj enega polimorfnega alela OPRM1 rs1799971 G in v tretjem tednu pri nosilkah vsaj enega polimorfnega alela OPRM1 rs677830 T. Prisotnost polimorfizma MIR107 rs2296616 je povečala tveganje za kronično bolečino, prisotnost polimorfizma MIR23B 1011784 je povečala tveganje za nevropatsko bolečino, prisotnost polimorfizma OPRM1 rs677830 pa je zmanjšala tveganje za nevropatsko bolečino. Vpliva polimorfizmov na jakost akutne bolečine nismo potrdili.

• Language: Slovenian
• Keywords: genotipizacija, genetska variabilnost, OPRM1, MIR23B, MIR107, tramadol, lajšanje bolečine, neželeni učinki
• Work type: Master's thesis/paper
• Organization: BF - Biotechnical Faculty
• Year: 2021
• PID: 20.500.12556/RUL-126334
• COBISS.SI-ID: 71771395
• Publication date in RUL: 17.04.2021

Secondary language

• Language: English
• Title: The impact of genetic variability in the opioid receptor mu 1 (OPRM1) gene on tramadol treatment outcome

Abstract

Mu opioid receptor encoded by OPRM1 is crucial for the analgesic effect of opioid drugs. It is the target of tramadol, a centrally acting opioid analgesic for the treatment of moderate to severe acute and chronic pain. Genetic polymorphisms of the OPRM1 and miRNA genes may affect the outcome of tramadol treatment due to altered expression or receptor sensitivity. The aim of this study was to determine the frequencies of OPRM1 rs1799971, OPRM1 rs677830, MIR23B 1011784 and MIR107 rs2296616 polymorphisms in the group of patients after breast cancer surgery. Genotyping with quantitative allele-specific polymerase chain reaction was performed to evaluate the impact of these polymorphisms on the severity of acute pain and the presence of adverse effects, chronic and neuropathic pain. Carriers of at least one polymorphic MIR107 rs2296616 A allele had a lower risk of nausea in the third week of treatment, and patients with MIR23B 1011784 GG genotype had a higher risk of nausea in the fourth week. A higher risk of constipation during the first month was confirmed in carriers of at least one polymorphic OPRM1 rs1799971 G allele and in the third week in carriers of at least one polymorphic OPRM1 rs677830 T allele. The presence of MIR107 rs2296616 polymorphism increased the risk of chronic pain, the presence of MIR23B 1011784 polymorphism increased the risk of neuropathic pain, and the presence of the OPRM1 rs677830 polymorphism reduced the risk of neuropathic pain. The effect of the polymorphisms on the intensity of acute pain has not been confirmed.

• Keywords: genotyping, genetic variability, OPRM1, MIR23B, MIR107, tramadol, pain treatment, adverse effects