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Neuropsychopharmacol Rep. 2018 Dec;38(4):175-181. doi: 10.1002/npr2.12030. Epub 2018 Sep 14.

Gamma-aminobutyric acid transaminase genetic polymorphism is a candidate locus for responsiveness to opioid analgesics in patients with cancer pain: An exploratory study.

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Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo, Japan.
Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Department of Surgery, Toho University Medical Center, Sakura Hospital, Chiba, Japan.



Cancer pain impairs not only physical functions but also social functions and roles. Consequently, the overall health-related quality of life of patients with cancer pain deteriorates. Opioid analgesics are recommended for treating moderate to strong cancer pain. Advances in human genome research have fueled a growing interest to understand individual differences in responsiveness to opioid analgesics. This study aimed to explore and identify novel loci for genes predisposing an individual to opioid analgesic responsiveness.


A total of 71 cancer patients rated their pain on an 11-point numerical rating scale twice before and after increasing opioid analgesics. A genomewide association study focusing on single nucleotide polymorphisms (SNPs) was conducted to associate pain decrease with increased dosage of opioid analgesics based on weight (ie, responsiveness to opioid analgesics). A genomewide significance (P < 5E-8) was set for multiplicity of analyses to control for false positives.


Two SNPs passed the genomewide threshold for significance. One exonic SNP (rs1641025) was located in the ABAT [4-aminobutyrate aminotransaminase (GABA transaminase)] gene on chromosome 16. The other SNP (rs12494691) was located on chromosome 3, which was not associated with any known genes. These SNPs were not associated with opioid-related adverse effects.


Our results preliminarily suggest that both SNPs might be potential candidate loci for responsiveness to opioid analgesics, and GABA transaminase might be a possible target for developing adjuvant pharmacotherapy with opioid analgesics in adjuvant pharmacotherapy. Our results should be validated in a large-scale study with a larger sample size.


genetics: human; pain: basic/clinical; pharmacogenetics: basic/clinical; responsiveness to opioid analgesics

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