Polymorphism of the COMT, OPRM1, CYP2D6, CYP2B6, CYP2C9 genes and effectiveness of analgesia in cardiac surgery

Introduction. A personalized medicine involving timely assessment of individual characteristics of patients is important in modern world. This assessment takes into account not only variable phenotypic traits but also various markers, including genetic markers. An important aspect of treatment after open-heart surgery is early rehabilitation that cannot be achieved without adequate and timely analgesia. Objective. To study the association of polymorphic markers of the COMT, OPRM1, CYP2D6, CYP2B6, and CYP2C9 genes with effectiveness of postoperative pain relief in open-heart surgery. Material and methods. A pilot observational study involved 90 patients who underwent cardiac surgery through median sternotomy. Postoperative multimodal anesthesia implied fentanyl, tramadol, paracetamol, and ketoprofen. Pain severity was daily assessed using digital rating scale at rest and coughing. Postoperative nausea, vomiting, itching, urinary retention, sedation and sensations around postoperative wound were also evaluated. Consumption of analgesics was measured postoperatively. A single molecular genetic analysis was performed to determine the alleles and genotypes of the following single nucleotide variants: rs1065852 of the CYP2D6 gene, rs1799971 of the OPRM1 gene, rs4680 of the COMT gene, rs2279343 of the CYP2B6 gene, rs1799853 of the CYP2C9 gene. Results. Current analgesia scheme for open heart surgery does not provide adequate pain relief within three postoperative days. Female gender was a predictor of duration and intensity of pain syndrome, as well as sedation depth. Among genetic markers, homozygous genotype AA rs4680 of the COMT gene identified in 54.5% of patients is of the greatest interest. However, it cannot be used as a predictor of pain intensity and analgesic consumption. In six months after surgery, 24.5% of patients with median sternotomy still experienced chest pain, and 13.2% reported QoL impairment. Conclusion. In the study group, 54.5% of patients were carriers of homozygous genotype AA rs4680 of the COMT gene. Clinical significance of this genetic polymorphism for evaluating the effectiveness of pain management in cardiac surgery is still a matter of debate and depends on specific analgesia regimen.