Distribution of CYP2D6 multiplication, CYP2D6*5, and clinical implications in postoperative patients receiving tramadol analgesia in the Minangkabau ethnic group, Indonesia

Abstract

Background Cytochrome P450 2D6 (CYP2D6) is an important enzyme that metabolizes commonly used drugs, such as tramadol hydrochloride (a widely used opioid analgesic). Genetic polymorphisms of CYP2D6 have been shown to influence the pharmacodynamic properties of administered drugs. This study aimed to screen 63 postoperative patients (wild-type, CYP2D6*5, and CYP2D6 multiplication) of Minangkabau ethnicity in West Sumatera, Indonesia, who received tramadol using a modified long PCR method, and to investigate the clinical impact of tramadol on these patients. This study had a retrospective clinical trial registry number NCT06642480. Methods The Reported Long PCR was modified using different DNA polymerases, optimizing annealing, and the number of step PCR to detect wild-type, CYP2D6*5, and multiplication CYP2D6. To ensure accurate PCR, the size of the PCR product was monitored: wild-type (5kb), CYP2D6*5 (6kb), and CYP2D6 multiplication genotype (10 kb). The wild-type PCR product was used as the internal control. The method was applied to screen 63 postoperative patients of Minangkabau ethnicity who received tramadol. The clinical impact was investigated and analyzed using analysis of variance (ANOVA) followed by a chi-square test. Result The Long PCR was successfully modified with a two-step PCR at 68°C °C as the annealing and extension temperatures. The screened genotype patients were dominated by the wild-type, followed by CYP2D6*5, and multiplication CYP2D6 with percentages of 89%, 6,3%, and 4,7% respectively. A total of 6.3% of CYP2D6*5 cases were classified as heterozygous and predicted as intermediate metabolizers. In addition, sex and age did not affect postoperative tramadol analgesia treatment, whereas weight had a significant impact (p=0.008). Conclusion The percentages of CYP2D6*5 and CYP2D6 multiplication genotypes were similar to those observed in another Asian population. Based on statistical analysis, tramadol was effective as an analgesic treatment for postoperative Minangkabau ethnicity patients with wild-type, CYP2D6*5, and multiple CYP2D6 genotypes. Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.