| The Correlation between Genetic Polymorphism of OPRM1 (A118G) and MDR1 (C3435T) with Analgesia and the Adverse Effects by Epidural Morphine. |
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Helen Ki Shinn, Tae Jung Kim, Hong Sik Lee, Ju Hee Kang, Jeong Uk Han, Hyun Kyoung Lim, Seung Hun Ryu, Jang Ho Song |
1Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea. snoguy@freechal.com
2Department of Pharmacology, Medicinal Toxicology Research Center, Inha University College of Medicine, Incheon, Korea.
3BK 21 Center for Advanced Medical Education, Inha University College of Medicine, Incheon, Korea. |
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| Abstract |
BACKGROUND
The effect of a single nucleotide polymorphism (SNP) of the micro-opioid receptor gene at nucleotide position 118 (OPRM1:118A > G) and the MDR1 gene (exon 26: C3435T) have an influence on the interindividual variability of clinical opioid pain therapy. This study aims to evaluate the correlation among pain control and side effects of epidural morphine and these pharmacogenetic modulators.
METHODS
194 patients who were undergoing abdominal surgery were included in the study. Patients received a morphine 2 mg bolus and 2 mg/day via epidural route. The VAS score and opioid side effects were checked at postoperative 6, 24 and 48 hr. Patients were genotyped for the known SNPs of the OPRM1 and MDR1. RESULTS: For the SNP of OPRM1, the mutated genotype frequency (homo-wild, heterozygous, and homo-mutants) were 36.8, 47.9 and 15.3%, respectively, and the mutated genotype frequencies for the MDR1 SNP were 46.7, 40.2 and 13.1%, respectively. There were no significant differences in the VAS scores and side effects among the three groups of OPRM1 and MDR1. Yet carriers of the mutated allele 3435 TT, CT of the MDR1 gene showed marginally greater significant sedation effects than did non-carriers (CC) (P = 0.065, the OR was 1.78, 95% CI 0.98-3.24, P = 0.059) and also a lower incidence of analgesic usage (P =0.058).
CONCLUSIONS
In our data there was a large difference in OPRM1 SNP allele frequency for the Korean population compared to other populations. The SNP of OPRM1 and MDR1 genes did not have significant altered clinical morphine analgesia and side effects via the epidural route. But the SNP of MDR1 gene is more sensitive genetic predictor of the clinical side effects (especially for sedation) and analgesic effects by opioid. |
| Key Words:
interindividual variability; morphine; opioid; pharmacogenetic; polymorphism |
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