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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.

Author information

1
Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo, Japan.
2
Department of Pain and Palliative Medicine, The University of Tokyo Hospital, Tokyo, Japan.
3
Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
4
Department of Surgery, Toho University Medical Center, Sakura Hospital, Chiba, Japan.

Abstract

AIM:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

PMID:
30277654
DOI:
10.1002/npr2.12030
[Indexed for MEDLINE]
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