Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer

  title={Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer},
  author={Ken-Ichi Fujita and Yuichi Ando and Wataru Yamamoto and Toshimichi Miya and Hisashi Endo and Yu Sunakawa and Kazuhiro Araki and Keiji Kodama and Fumio Nagashima and Wataru Ichikawa and Masaru Narabayashi and Yuko Akiyama and Kaori Kawara and Mari Shiomi and Hiroyasu Ogata and Hiroyasu Iwasa and Yasushi Okazaki and Takashi Hirose and Yasutsuna Sasaki},
  journal={Cancer Chemotherapy and Pharmacology},
PurposeTo investigate the effects of genetic polymorphisms on morphine-induced adverse events in cancer patients.MethodsWe examined the relation of morphine-related adverse events to polymorphisms in UDP-glucuronosyltransferase (UGT) 2B7, ATP-binding cassette, sub-family B, number 1 (ABCB1), and μ-opioid receptor 1 genes in 32 Japanese cancer patients receiving oral controlled-release morphine sulfate tablets.ResultsThe T/T genotype at 1236 or TT/TT diplotype at 2677 and 3435 in ABCB1 was… 

Influence of UGT2B7, OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption

It is concluded that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.

Gene polymorphisms of OPRM1 A118G and ABCB1 C3435T may influence opioid requirements in Chinese patients with cancer pain.

The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioid requirements in Chinese cancer pain patients and may possibly extend to the ABCB1 C3435T SNP.

The impact of UGT2B7 C802T and CYP3A4*1G polymorphisms on pain relief in cancer patients receiving oxycontin

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Association of ABCC2 genotype with efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.

It is found that the -24C>T polymorphism in the ABCC2 gene was significantly associated with the efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.

ABCC3 and OCT1 genotypes influence pharmacokinetics of morphine in children.

The data suggest that besides bodyweight, OCT1 and ABCC3 genotypes play a significant role in the pharmacokinetics of intravenous morphine and its metabolites in children.

Association of ABCC 2 Genotype with Ef fi cacy of First-line FOLFIRI in Japanese Patients with Advanced Colorectal Cancer

It is found that the 124C>T polymorphism in the ABCC2 gene was significantly associated with the efficacy of first-line FOLFIRI in Japanese patients with advanced colorectal cancer.

OPRM1 and ABCB1 polymorphisms and their effect on postoperative pain relief with piritramide.

Variation OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide, which leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects.

ABCB1 Polymorphisms and Cold Pressor Pain Responses: Opioid-Dependent Patients on Methadone Maintenance Therapy

This study provides the first evidence that ABCB1 polymorphisms are associated with cold pressor pain responses among Malay male patients with opioid dependence on MMT and may provide an initial prediction on heightened pain sensitivity or hyperalgesia for individuals who are carriers of the ABCB 1 polymorphisms.

Effect of UGT2B7 -900G>A (-842G>A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort.

It is illustrated that in addition to gestational and postnatal age, the UGT2B7 -900G>A polymorphism significantly alters morphine pharmacokinetics in preterm infants.

Association Study between Genes Related to Pharmacokinetics and Pharmacodynamics of Oxycodone and Response to Drug Treatment: A Genetic Cohort Study

It is suggested that genetic polymorphisms of genes related to pharmacokinetics and pharmacodynamics of oxycodone have a potential impact on clinical responses to drug in cancer patients with pain.



Association of ABCB1/MDR1 and OPRM1 Gene Polymorphisms With Morphine Pain Relief

Combining the extreme genotypes of both genes, the association between patient polymorphism and pain relief improved, allowing the detection of three groups: strong responders, responders, and non‐responders, with sensitivity close to 100% and specificity more than 70%.

Sequence variability and candidate gene analysis in two cancer patients with complex clinical outcomes during morphine therapy.

Genetic differences in two morphine-related gene sequences, UDP-glucuronosyltransferase 2B7 (UGT2B7) and mu opioid receptors (MOR1), in two cancer patients whose clinical responses to morphine were very different are presented.

Allelic Expression Imbalance of Human mu Opioid Receptor (OPRM1) Caused by Variant A118G*

Results indicate that OPRM1-G118 is a functional variant with deleterious effects on both mRNA and protein yield, and clarifying the functional relevance of polymorphisms associated with susceptibility to a complex disorder such as drug addiction provides a foundation for clinical association studies.

Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1.

Patients with drug-resistant epilepsy were more likely to have the CC genotype at ABCB1 3435 than the TT genotype, implying that the polymorphism may not itself be causal but rather may be linked with the causal variant.

Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo.

A significant correlation of a polymorphism in exon 26 (C3435T) of MDR-1 with expression levels and function is observed and this polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of M DR-1.

An MDR1-3435 variant is associated with higher plasma nelfinavir levels and more rapid virologic response in HIV-1 infected children

HIV-1 infected children with the MDR1-3435-C/T genotype had more rapid virologic responses to HAART at week 8 with higher plasma nelfinavir concentrations compared to those with the C/C genotype.

Pharmacogenetics of Opioids

The role of pharmacogenomics in mediating interpatient variability in efficacy and side effects to this important class of drugs will be better informed as knowledge regarding the interplay between genes affecting opioid pharmacokinetics including cerebral kinetics and pharmacodynamics increases.