The human mu-opioid receptor gene (OPRM1) contains a functional single nucleotide polymorphism (SNP), A118G, which has been associated with altered opioid addiction risk, however the mechanisms responsible for this are not well understood.
<i>OPRM1</i> nonsynonymous single nucleotide polymorphism rs1799971 (A118G) is the most prominent candidate due to its significant association with onset and treatment of opioid addiction.
The OPRM1 (rs1799971) polymorphism was investigated in an association study of a group of ADS patients (n = 177) and in subgroups (delirium tremens and/or seizures, age at onset <26 years, dissocial alcoholics, positive familial history of alcoholism, delirium tremens, and seizures).
The OPRM1 A118G single nucleotide polymorphism (SNP rs1799971) gene variant encoding the N40D µ-opioid receptor (MOR) has been associated with dependence on opiates and other drugs of abuse but its mechanism is unknown.
Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans.
Susceptibility to opioid addiction is associated with variants in the gene encoding the MOR, <i>OPRM1</i> Varying with ethnicity, ∼25% of humans carry a single nucleotide polymorphism (SNP) in <i>OPRM1</i> (A118G).
Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9.30, 95% CI: -17.25 to -1.35, p = 0.02) and OPRM1 rs1799971 (G allele, β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17-3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48-0.99, p = 0.046).
The AA genotype of rs4680 or A_T_C_A/ A_T_C_A (rs6269_rs4633_ rs4818_rs4680) diplotype of COMT, combined with the AG genotype of OPRM1 A118G, showed significantly increased pressure pain threshold from butorphanol.
In subgroup analysis, we did not find statistically significant correlation between OPRM1 A118G polymorphism and opioid pain relief among Caucasian patients (SMD=-0.15; 95% CI, -0.29 to -0.00; P=0.04), as well as among morphine users (SMD =-0.20; 95% CI, -0.40 to 0.00, P=0.05), except for Asian patients (SMD=-0.42; 95% CI, -0.62 to -0.23; P<0.001).
There was no significant difference in duration of epidural fentanyl analgesia for the three SNVs (161±68 and 143±51 min for wild type and allele carriers of the 118A>G SNV respectively [P=0.08]).
In comparison, two pain-related gene SNPs (OPRM1 [rs1799971] and COMT [rs4818]) interacted with psychological factors to predict four shoulder impairment phenotypes (abduction: 5-day average loss; strength loss: 5-day average, peak, and relative loss).
The aim of this study was therefore to address the interaction between the single nucleotide polymorphisms opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 on placebo analgesia.
Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118Grs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h.
Individuals (n = 146) meeting DSM-IV criteria for alcohol dependence who were genotyped for the OPRM1 A118G SNP and who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16-week clinical trial.