Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents

Abstract

The μ1 opioid receptor (OPRM1) genetic variant A118G results in decreased μ-receptor binding potential in the brain and increases morphine requirement. We hypothesized that OPRM1 A118G polymorphism will affect morphine-induced respiratory depression (MIRD) risk in children receiving morphine. A prospective genotype-blinded study was conducted in 88 healthy adolescents (11-18 years; 67% female, 85% Caucasian) who underwent spine fusion for scoliosis. They were followed for 48 h postoperatively for MIRD, pain scores, morphine consumption and use of analgesic adjuvants. Patients were genotyped for OPRM1 A118G variant-76% were wild type (AA) and 24% heterozygous/homozygous for variant (AG/GG). Multivariable logistic regression showed that the risk of MIRD in patients with AA genotype was significantly higher (odds ratio 5.6, 95% CI: 1.4-37.2, P=0.030). Presence of G allele was associated with higher pain scores (effect size 0.73, P=0.045). This novel association is an important step toward predicting MIRD susceptibility and personalizing morphine use.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1

Incidence of morphine-induced respiratory depression in the two genotype groups (AA and AG+GG) for A118G polymorphism of the OPRM1 gene. The incidence was significantly higher in the AA subgroup (25/67 or 37%) compared with AG+GG subgroup (2/21 or 0.09%) (P =0.016).

Figure 2

Comparison of the OPRM1 genotype subgroups (AA versus AG+GG) at the A118G variant with respect to pain scores and morphine requirements in the first two postoperative days after spine surgery. Mean pain scores were significantly higher in the AG +GG subgroup (P =0.024).

Figure 3

Mean pain scores and morphine consumption over time epochs along with standard error of means (tails) are presented by OPRM1 genotype for the A118G variant. The data at each time point (in hours) describes the cumulative measure collected during that interval after surgery. Pain scores were significantly higher for AG +GG group (compared with AA) at 2 h (P =0.04), 8 h (P =0.02) and 40 h (P =0.04); and morphine consumption was also significantly higher for AG+GG at 2 h (P =0.02) and 16 h (0.02).

Figure 4

Risk of morphine-induced respiratory depression in the first two postoperative days for the two genotype groups (AA and AG+GG) of the OPRM1 A118G polymorphism. Odds ratio and 95% confidence intervals are given. This is a dominant genetic model assuming OR of 1 for the AG+GG genotypes.