The Studied Gene-Drug Interaction
Long-standing opioid maintenance is largely the cost-effective method of dealing with reliance on an opioid. Then again, the nontoxic and successful utilization of replacement opioids, for example, methadone depends on an immense deal on the best dosage that lessens withdrawal and unpleasant opioid side effects, and simultaneously cuts down the use of heroin. The thin therapeutic index and disparities in individual response to drugs further complicate this treatment process. According to Barratt, Coller, Hallinan, Byrne, White, Foster, and Somogyi (2012), Australia witnesses high incidences in methadone maintenance plans notwithstanding the personalized treatment tactics it employs (comparison of the patient’s indications and the dosage of drug). For this reason, a profound comprehension of factors lying behind personal reactions to methadone is of extreme consequence. Such knowledge is helpful in enhancing treatment and enriching clinical effectiveness.
There is genetic inconsistency in the ABCB1 gene, which encodes the P-Glycoprotein efflux carrier (Barratt et al., 2012). This gene is associated with changes in the doses needed to maintain methadone levels during therapy. Previous studies indicate proof of a possible interaction between OPRM1 (encodes the receptor of the mu opioid) and ABCB1 to influence reaction to morphine in a contradictory manner (Barratt et al., 2012). This research aspires to establish if such gene to gene relation transpires for methadone during methadone maintenance therapy.
Study Design and Conclusions
The study subjects 119 individuals who depend on opioids to a genotypic examination to test for the presence of five single nucleotide polymorphisms of the gene ABCB1 and OPRM1. These are the 61A>G, 1199G>A, 1236C>T, 2677G>T, and 3435C>T, in addition to OPRM1 118A>G (Baratt et al., 2012). The study uses polymerase chain reaction in determining the genotypes. Restriction fragment length polymorphism is then carried out. According to Barratt et al., Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) spots the 2677G>T via the Cascorbi et al. technique (2012). An agarose gel electrophoresis assists in the visualization of the digested portions. For OPRMI, the 118A>G phenotype utilizes allele-specific polymerase chain reaction. The original case study records provide patient information on dose, pharmacokinetics, and demography. Noteworthy differences unrelated to glycoprotein P have a likely effect on absorption, distribution, breakdown, and removal of methadone. For this reason, the research also investigates “the trough plasma (R) methadone concentrations (Ctrough ng/mL)” (Barratt et al., 2012).
The research identifies 84 subjects with Ctrough data and includes them in pharmacokinetic scrutiny. Utilization of the Chi-square tests obtains genotype deviations from the Hardy-Weinberg equilibrium whereas version 1 of the PHASE software suggests the ABCB1 haplotypes from genotype data (Barratt et al., 2012).
The frequencies of OPRMI1 and ABCB1 fall within the Hardy-Weinberg equilibrium of P≥0.4 (Barratt et al., 2012). The study observes 12 diverse haplotypes out of the 114 haplotypes that it positively establishes. There are no substantial dissimilarities between the wild-type genes and methadone dosages in OPRMI1 and ABCB1 (Barratt et al., 2012).
How this Article Adds to the Body of Knowledge on Pharmacogenetics
Pharmacogenetics studies individual responses to drugs in relation to their genetic constituents (Zdanowicz, 2010). Pharmacogenomic studies hope to augment drug efficiency and get rid of unsolicited side effects of medications in the course of therapy (2010). Previous studies establish the effect of the genetics of metabolic enzymes on the deactivation of drugs. Records of numerous genetic deviations in vital liver enzymes that break down drugs in the early 1970s steer the development of this discipline. Ten outstanding pharmaceuticals and the Wellcome Trust pool efforts to establish 1.8 million Single Nucleotide Polymorphisms (SNPs). According to Zdanowicz, the NIH (National Institutes of Health) found the Pharmacogenetics Research Network (PGRN) with three main aims including scrutinizing the consequences of genetic differences on drug reaction (2010).
This study, therefore, contributes to the achievement of this target by establishing that there is no considerable gene to gene interaction between OPRM1 and ABCB1 genes on the function of methadone. This helps in providing specialized treatment to patients requiring methadone maintenance treatment.
References
Barratt, D. T., Coller, J. K., Hallinan, R., Byrne, A., White, J. M., Foster, D. J. R., & Somogyi, A. A. (2012). ABCB1 haplotype and OPRM1 118A, G genotype interaction in methadone maintenance treatment pharmacogenetics. Pharmacogenomics and Personalized Medicine. 1(5), 53-62. Web.
Zdanowicz, M. M. (2010). Pharmacogenomics: Past, present, and future. In M. M. Zdanowicz (Ed.), Concepts in pharmacogenomics (pp. 3-18). USA: American Society of Health-System Pharmacists Inc.