The research progress of microRNA on regulation of drug disposition in vivo / 中国药理学通报

The disposition of drug in vivo is subjected to a series of biotransformation and transport, depending on the involvement of drug-metabolizing enzymes and transporters.However, the individual capacity varies when metabolizing and transporting the same drug, and pharmacogenomics has trouble in completely explaining the differences.microRNA, a key aspect of epigenetic modifications, is a powerful complement to traditional genetics.Emerging evidences have confirmed that drug-metabolizing enzymes and transporters be controlled by different microRNAs, and the same microRNA also regulates several drug-metabolizing enzymes or/and transporters simultaneously.All of these researches infer that microRNAs are likely to realize the comprehensive macro-regulation of gene expression.The further study of microRNAs maybe a suitable point to research the interindividual variability in disposition of drugs, and it provides a theoretical basis for rational use of drug and individualized medicine.

The Correlation between Genetic Polymorphism of OPRM1 (A118G) and MDR1 (C3435T) with Analgesia and the Adverse Effects by Epidural Morphine / 대한마취과학회지

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.

Advances in pharmacogenetics of anti-Parkinson's drugs treatment / 中国药理学通报

Parkinson's disease(PD)is a neurodegenerative disease that predominantly affects the elderly.Dopamine mimicking drug is the mainstay in the treatment of Parkinson's disease.However,there is a large of interindividual variability in response to anti-Parkinson's disease drugs.It is thought that genetic variability in dopamine system genes is one of the important factors in determining interindividual variability in drug response.There are a lot of studies focused on the relationship between the risk of Parkinson's disease and genetic variations in domestic,while it is a lack of the pharmacogenetics study on Parkinson's disease.This review summarizes the relationship between the polymorphism of genes encoding dopamine transporter,dopamine-metabolizing enzymes and dopamine receptors and Parkinson's disease treatment.