The Dopamine Receptor 2 (DRD2) gene is associated with opioid-induced nausea and emesis

Abstract

Opioids remain a preferred treatment for moderate to severe pain; however, side effects represent a significant concern. Among the most common and distressing adverse effects are nausea and vomiting. DRD2 are known to contribute to opioid-induced emesis in humans with; therefore, we examined the associations of DRD2 polymorphisms with side effects after morphine and pentazocine administration. 115 participants underwent intravenous administration of morphine (.08 mg/kg) and 100 were administered pentazocine (.5 mg/kg). Nausea and emesis reported by the participant and observed by the research nurse were recorded. Also, participants completed somatic side effects (SSE) and cognitive-affective side effects (CASE) questionnaires after drug administration. Three single nucleotide polymorphisms (SNPs) of DRD2 (rs1800497, rs6279 and rs2734838) were genotyped. Associations of individual SNPs and haplotypes with nausea and emesis were examined. Chi-square-test and logistic regression were used to analyze the alleles, and a model based on the risk haplotypic structure implemented with the Expectation-maximization algorithm was used to analyze the data. The rs1800497 SNP was significantly associated with morphine-induced nausea and emesis (p < .05). Specifically, homozygotes for the minor allele experienced significantly greater nausea and emesis and had higher SSE and CASE scores. The rs6279 SNP (p < 0.05) was associated with emesis as well as SSE and CASE scores after pentazocine. The haploblock analysis formed by two SNP showed that when rs1800497 rs6279 was combined the double presence of the haplotype [AC] was significantly associated with nausea (p = 0.0460) and emesis (p = 0.0056) after morphine. The analysis formed by the three SNPs showed that the haplotype [ACA] was significantly associated with nausea (p = 0.0277) and emesis (p = 0.0019) after morphine. Allelic variation at the DRD2 locus may increase the risk of nausea, emesis, somatic and cognitive effects after administration of morphine and pentazocine. Additional research is warranted to replicate and extend these results to a clinical population. Opioids remain a preferred treatment for moderate to severe pain; however, side effects represent a significant concern. Among the most common and distressing adverse effects are nausea and vomiting. DRD2 are known to contribute to opioid-induced emesis in humans with; therefore, we examined the associations of DRD2 polymorphisms with side effects after morphine and pentazocine administration. 115 participants underwent intravenous administration of morphine (.08 mg/kg) and 100 were administered pentazocine (.5 mg/kg). Nausea and emesis reported by the participant and observed by the research nurse were recorded. Also, participants completed somatic side effects (SSE) and cognitive-affective side effects (CASE) questionnaires after drug administration. Three single nucleotide polymorphisms (SNPs) of DRD2 (rs1800497, rs6279 and rs2734838) were genotyped. Associations of individual SNPs and haplotypes with nausea and emesis were examined. Chi-square-test and logistic regression were used to analyze the alleles, and a model based on the risk haplotypic structure implemented with the Expectation-maximization algorithm was used to analyze the data. The rs1800497 SNP was significantly associated with morphine-induced nausea and emesis (p < .05). Specifically, homozygotes for the minor allele experienced significantly greater nausea and emesis and had higher SSE and CASE scores. The rs6279 SNP (p < 0.05) was associated with emesis as well as SSE and CASE scores after pentazocine. The haploblock analysis formed by two SNP showed that when rs1800497 rs6279 was combined the double presence of the haplotype [AC] was significantly associated with nausea (p = 0.0460) and emesis (p = 0.0056) after morphine. The analysis formed by the three SNPs showed that the haplotype [ACA] was significantly associated with nausea (p = 0.0277) and emesis (p = 0.0019) after morphine. Allelic variation at the DRD2 locus may increase the risk of nausea, emesis, somatic and cognitive effects after administration of morphine and pentazocine. Additional research is warranted to replicate and extend these results to a clinical population.